Thiazolidinone compounds and their use in the treatment of psychiatric or neurological disorders and inflammation, in particular neuroinflammation

ABSTRACT

The invention relates to a compound comprising the following general formula (1): 
     
       
         
         
             
             
         
       
     
     and said compound for use as a medicament, in particular for use in the treatment psychiatric or neurological disorders and inflammation, in particular neuroinflammation: (formula 1) wherein each of R1, R2 and R3 are selected independently from each other from alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, or heteroaryl.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a divisional of U.S. patent application Ser. No. 15/314,067filed Nov. 26, 2016; which is the US national stage of InternationalApplication No. PCT/EP2015/061915, filed May 28, 2015, and which in turnclaims the benefit of EP Patent Application Nos. 14171024.4 filed onJun. 3, 2014 and 14170449.4 filed on May 28, 2014. The contents of theforegoing patent applications are incorporated by reference herein intheir entirety.

FIELD OF THE INVENTION

The present invention relates to a class of thiazolidinone derivativesas anandamide cellular uptake inhibitors and their use in the treatmentof psychiatric or neurological disorders and inflammation, in particularneuroinflammation.

BACKGROUND OF THE INVENTION

The endocannabinoid system (ECS) is a lipid signaling system comprisingendocannabinoids (ECs), which are lipids derived from arachidonic acid,the G-protein-coupled cannabinoid receptors CB1 and CB2, as well asseveral other actual and potential physiological targets involved in thesynthesis, transport and degradation of ECs. The major ECs are2-arachidonoylglycerol (2-AG) and N-arachidonoyl ethanolamide (AEA;anandamide) which modulate synaptic transmission by retrograde signalingvia CB1 receptors and exert potent immunomodulatory effects via both CB1and CB2 receptors. The ECS has been implicated in physiological andpathophysiological conditions including inflammation, pain, psychiatricdisorders and metabolic reprogramming. The ECS provides a primaryon-demand protection system against acute excitotoxicity in the centralnervous system (CNS) (Marsicano et al., 2003, Science, 302, 84-8.)

Therapeutic strategies within the ECS include the use of cannabinoidreceptor agonists and antagonists, blockage of hydrolytic enzymesdegrading ECs, such as fatty acid amide hydrolase (FAAH) andmonoacylglycerol lipase (MAGL), as well as inhibition of EC cellmembrane trafficking. Although so far no membrane protein for ECtransport has been identified, several lines of evidence suggest afacilitated membrane transport involving both membrane and cytoplasmictargets (Chicca et al., 2012, J Biol Chem. 287, 36944-67; Fowler CJ.,2013, FEBS J., 280:1895-904). The movement of AEA across the cell isaffected by the concentration gradient enhanced by rapid intracellularhydrolysis of AEA catalyzed by FAAH. Therefore, FAAH plays a key role inAEA cellular uptake by generating an inward concentration gradient forAEA, which is the major driving force for its cellular uptake.

Using the commercially available AEA uptake inhibitors UCM707, OMDM-2and LY2183240 evidence for bidirectional transport of both AEA and 2-AGacross cell membranes, as well as a common mechanism of cellularmembrane transport for all arachidonate-based ECs was recently provided(Chicca et al., 2012, J Biol Chem. 287, 36944-67). Since all of theavailable inhibitors are only moderately potent and show low selectivitytowards AEA transport inhibition over FAAH inhibition or othercytoplasmic targets, investigations of the mechanisms of AEA and 2-AGcellular uptake are hampered by a lack of adequate tools. As indicatedby a recent study (Nicolussi et al., Pharmacol Res., 2014, 80:52-65),the CNS pharmacology of inhibitors of endocannabinoid breakdown andinhibitors of endocannabinoid membrane transport is distinctly differentand that inhibition of FAAH and AEA cellular uptake, respectively, canbe independent from each other. Prior art has shown the use ofDodeca-2E,4E-diene amides as specific AEA cellular uptake inhibitors asanti-inflammatory agents in skin (WO 2010136221 A1). The potentialtherapeutic value of specific AEA cellular uptake inhibitors to treatCNS related diseases remains largely unknown. In a murine model ofmultiple sclerosis, the AEA cell membrane transport and FAAH inhibitorUCM707 showed beneficial effects by reducing microglial activation(Ortega-Gutierrez et al., 2005, FASEB J., 19, 1338-40). Using UCM707, itwas shown that an increased AEA tone limits excitotoxicity in vitro andin a model of multiple sclerosis (Loria et al., 2010, Neurobiol Dis.,37, 166-76). The non-specific AEA cellular uptake and FAAH inhibitorAM404 was shown to reduce the rewarding effects of nicotine andnicotine-induced dopamine elevations in the nucleus accumbens shell inrats (Sherma et al., Br J Pharmacol., 2012, 165, 2539-48). Thenon-specific AEA cell membrane transport inhibitor VDM-11 was shown tomodulate sleep and c-Fos expression in the rat brain (Murillo-Rodriguezet al., Neuroscience, 2008, 157, 1-11). The administration of AEA cellmembrane transport inhibitors OMDM-2 or VDM-11 was shown to promotesleep and decreases extracellular levels of dopamine in rats(Murillo-Rodriguez et al., Physiol Behav. 2013, 109, 88-95). UCM707 wasshown to behave as a symptom control agent in models of Huntington'sdisease and multiple sclerosis, but failed to delay/arrest theprogression of different motor-related disorders (de Lago et al., EurNeuropsychopharmacol., 2006, 16, 7-18). As shown by a study using UCM707and AM404, AEA transport inhibitors may have potential in the treatmentof painful diabetic neuropathy (Hasanein and Soltani, 2009, Clin ExpPharmacol Physiol. 36, 1127-31). Targeting fatty acid binding protein(FABP) intracellular AEA carriers has recently been suggested to be astrategy to generate anti-inflammatory and anti-nociceptive drugs(Berger et al., 2012, PLoS One., 7(12):e50968.). However, thepharmacology between the inhibition of AEA cell membrane transport andthe inhibition of cytoplasmic carriers is expected to be different, asexemplified by the fact that FABP5 inhibitors do apparently not show thesame degree of cannabimimetic effects observed with the potent AEA cellmembrane transport inhibitor guineensine (Kaczocha et al., PLoS One.2014, 9(4):e94200; Nicolussi et al., 2014, Pharmacol Res., 80, 52-65).

Overall, there is a need for novel inhibitors of AEA cell membranetransport with superior specificity and potency to address CNS andinflammation related diseases involving aberrant endocannabinoid tone orin which AEA cellular uptake inhibition can target pathophysiologicalconditions. Given the fact that AEA and other endocannabinoids areinvolved in both synaptic processes via retrograde signaling andimmunomodulatory processes, specific inhibitors of AEA cell membranetransport are expected to exert therapeutic effects in neuropsychiatricdiseases involving neuroinflammation. When the degradation of AEA andother endocannabinoids is blocked, for example by covalent inhibition ofFAAH, the resulting intracellular accumulation of AEA (Chicca et al.,2012, J Biol Chem., 287, 36944-67) is expected to potentially also haveproinflammatory effects via oxygenation of AEA and possibly otherendocannabinoids by cyclooxygenase-2 (discussed in Chicca et al, 2014,ACS Chem Biol, http://pubs.acs.org/doi/abs/10.1021/cb500177c).Therefore, the inhibition of degradation of AEA and the inhibition ofcell membrane transport are distinct pharmacological interventions.Moreover, specific inhibition of AEA cell membrane transport, unlikeinhibition of FAAH or cytoplasmic carriers, is expected todifferentially modulate the AEA tone without leading to activation ofTRPV1 channels via intracellular AEA accumulation.

Our attention, therefore, is focused on the identification of new classof molecules able to specifically inhibit AEA cellular uptake that donot affect hydrolytic enzymes, such as the serine hydrolase FAAH. Weshow that these compounds trigger cannabimimetic behavioral effects andinhibit inflammation, in particular neuroinflammation.

The present invention relates to thiazolidinone derivatives and theiruse for the treatment of psychiatric or neurological disorders andinflammation, in particular neuroinflammation. The use of the compoundsof the invention in a method for treatment of psychiatric orneurological disorders is related to attenuation of neuroinflammationand neuronal retrograde signaling mediated via AEA and otherendocannabinoids. In example, such diseases include multiple sclerosis,epilepsy, Alzheimers disease, bipolar diseases, schizophrenia, sleepingdisorders, and spinal cord injury (Ashton and Moore, Acta PsychiatrScand. 2011, 124, 250-61; Aso and Ferrer I, Front Pharmacol., 2014, 5,37; Correa et al. Vitam Horm. 2009, 81, 207-30; Hofmann and Frazier, ExpNeurol. 2013, 244, 43-50; Pacher et al., Pharmacol Rev., 2006, 58,389-462).

SUMMARY OF THE INVENTION

A first aspect of the invention relates to a compound characterized by ageneral formula 1

-   -   wherein    -   R¹ is selected from        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl, and    -   each of R² and R³ are selected independently from each other        from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl.

A second aspect of the invention relates to a compound characterized bya general formula 1

-   -   wherein    -   R² is selected from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl, and    -   each of R¹ and R³ are selected independently from each other        from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl.

A third aspect of the invention relates to a compound characterized by ageneral formula 1

-   -   wherein    -   R³ is selected from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl, and    -   each of R¹ and R² are selected independently from each other        from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl.

A fourth aspect of the invention relates to a compound characterized bythe following general formula (1)

-   -   wherein    -   R¹ is selected from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl, and    -   each of R² and R³ are selected independently from each other        from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl.

A fifth aspect of the invention relates to a compound according to thefirst, second, third or fourth aspect of the invention for use as amedicament.

A sixth aspect of the invention relates to a compound according to thefirst, second, third or fourth aspect of the invention for use in thetreatment of psychiatric or neurological disorders and inflammation, inparticular neuroinflammation.

A seventh aspect of the invention relates to a pharmaceuticalpreparation for use in the treatment of psychiatric or neurologicaldisorders and inflammation, in particular neuroinflammation, comprisingat least one compound according to the first, second, third or fourthaspect of the invention.

A eight aspect of the invention relates to the compound of the firstaspect, particularly the first, second and third sub aspect, of theinvention for use as an endocannabinoid system modulator.

A ninth aspect of the invention relates to the compound of the firstaspect, particularly the first, second and third sub aspect, of theinvention for use as an AEA uptake Inhibitor.

DETAILED DESCRIPTION OF THE INVENTION

The compounds of the invention may also be used as an analgesic.Reference is made to the figures and experimental section.

The term “substituted” refers to the addition of a substituent group toa parent moiety.

“Substituent groups” can be protected or unprotected and can be added toone available site or to many available sites in a parent moiety.Substituent groups may also be further substituted with othersubstituent groups and may be attached directly or by a linking groupsuch as an alkyl, an amide or hydrocarbyl group to a parent moiety.“Substituent groups” amenable herein include, without limitation,halogen, oxygen, nitrogen, sulphur, hydroxyl, alkyl, alkenyl, alkynyl,acyl, carboxyl, aliphatic groups, alicyclic groups, alkoxy, substitutedoxy, aryl, aralkyl, amino, imino, amido fluorinated compounds etc.

As used herein the term “alkyl,” refers to a saturated straight orbranched hydrocarbon moiety containing in particular up to 12 carbonatoms. Examples of alkyl groups include, without limitation, methyl,ethyl, propyl, butyl, isopropyl, n-hexyl, octyl, and the like. Alkylgroups typically include from 1 to about 12 carbon atoms (C₁-C₁₂ alkyl).

As used herein the term “cycloalkyl” refers to an interconnected alkylgroup forming a saturated or unsaturated (or partially unsaturated) ringor polyring structure containing 3 to 10, particularly 5 to 10 carbonatoms. Examples of cycloalkyl groups include, without limitation,cyclopropane, cyclopentane, cyclohexane, norbornane, decaline oradamantan (Tricyclo[3.3.1.1]decan), and the like. Cycloalkyl groupstypically include from 5 to 10 carbon atoms (C₅-C₁₀ cycloalkyl).

Alkyl or cycloalkyl groups as used herein may optionally include furthersubstituent groups. A substitution on the cycloalkyl group alsoencompasses an aryl, a heterocycle or a heteroaryl substituent, whichcan be connected to the cycloalkyl group via one atom or two atoms ofthe cycloalkyl group.

As used herein the term “alkenyl,” refers to a straight or branchedhydrocarbon chain moiety containing in particular up to 12 carbon atomsand having at least one carbon-carbon double bond. Examples of alkenylgroups include, without limitation, ethenyl, propenyl, butenyl,1-methyl-2-buten-1-yl, dienes such as 1,3-butadiene and the like.Alkenyl groups as used herein may optionally include further substituentgroups.

As used herein the term “alkynyl,” refers to a straight or branchedhydrocarbon moiety containing in particular up to 12 carbon atoms andhaving at least one carbon-carbon triple bond. Examples of alkynylgroups include, without limitation, ethynyl, 1-propynyl, 1-butynyl, andthe like. Alkynyl groups as used herein may optionally include furthersubstituent groups.

As used herein the term “alkoxy,” refers to an oxygen alkyl moietycontaining in particular 1 to 12 carbon atoms comprising at least oneoxygen moiety instead of a CH₂ moiety. Examples of alkoxy groups includewithout limitation, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy,sec-butoxy, tert-butoxy, n-pentoxy, neopentoxy, n-hexoxy and the like.Alkoxy groups as used herein may optionally include further substituentgroups. Furthermore, “alkoxy” groups include straight or branched ethergroups (e. g. —CH₂—CH₂—O—CH₃) or polyether groups, which compriseseveral interconnected momomere alkoxy groups (e. g. —O—CH₂—CH₂—O—CH₃).

As used herein the term “heterocycle” refers to an interconnected alkylgroup forming a saturated or unsaturated ring or polyring structurecontaining 3 to 10, particularly 5 to 10 carbon atoms in which at leastone carbon atom is replaced with an oxygen, a nitrogen or a sulphur atomforming a nonaromatic structure. Heterocyclic groups as used herein mayoptionally include further substituent groups. A substitution on theheterocyclic group also encompasses an aryl, a cycloalkyl or aheteroaryl substituent, which can be connected to the heterocyclic groupvia one atom or two atoms of the heterocyclic group (comparable toindole).

As used herein the term “aryl” refers to a hydrocarbon with alternatingdouble and single bonds between the carbon atoms forming an aromaticring structure, in particular a six (C₆ to ten (C₁₀) membered ring orpolyring structure. The term “heteroaryl” refers to aromatic structurescomprising a five to ten membered ring or polyring structure, comparableto aryl compounds, in which at least one member is an oxygen or anitrogen or a sulphur atom. Due to simplicity reasons they aredenominated C₅ to C₁₀ heteroaryl, wherein at least one carbon atom isreplaced with an oxygen, a nitrogen or a sulphur atom forming anaromatic structure. For example a C₅ heteroaryl comprises a fivemembered ring structure with at least one carbon atom being replacedwith an oxygen, a nitrogen or a sulphur atom. Aryl or hetero aryl groupsas used herein may optionally include further substituent groups. Asubstitution on the hetero aryl group also encompasses an aryl, acycloalkyl or a heterocycle substituent, which can be connected to thehetero aryl via one atom or two atoms of the hetero aryl group(comparable to indole). The same applies to an aryl group.

As used herein “*” indicates a center of a E- or Z-isomer structure,which is located on the atom below the asterisk *.

According to a first aspect of the invention, the invention relates to acompound characterized by a general formula 1

-   -   wherein    -   R¹ is selected from        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₀₁ heteroaryl, and    -   each of R² and R³ are selected independently from each other        from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl.

In some embodiments, R¹ comprises the general formula 2a′ to 2j′,

-   -   with D being a C₁ to C₄ alkyl,    -   with each T being selected independently from each other from        —CH₂, —NH, —S, —O, —CHCH₃, —C(CH₃)₂ or —NR^(c), in particular        from NH, —S or —O, and    -   with T′ being selected from —CH₂, —NH, —S, —O, —CHCH₃, —C(CH₃)₂        or —NR^(c), and with each T″ being selected independently from        each other from being selected from —CH or ═N,    -   with R⁴ and R⁵ being selected independently from each other from        —H, —F, —CH₃, —CH₂CH₃, —OCH₃, —CH₂CF₃, —CHFCF₃, —CF₂CF₃, —CHF₂,        —CH₂F or —CF₃, in particular with R⁵ and R⁶ being selected        independently from each other from H, —F or —CH₃, and    -   with R⁶ being selected from —OH, —OCH₃, —OCH₂CH₃, —CH₃ or H,    -   with R⁷ being selected from ═NH, ═S or ═O, in particular from O,        and    -   with n of Z¹ _(n) being 0, 1, 2 or 3, in particular n of Z¹ _(n)        being 0 or 1, and with each Z¹ independently from any other Z¹        being selected from —F, —Cl, —Br, —I, CN, —R^(a), —OR^(a),        —(CH₂)_(r)OR^(a), —SR^(a), —(CH₂)_(r)SR^(a) or —NR^(a) ₂, with        each R^(a) being selected independently from each other from H,        a substituted or unsubstituted C₁-C₈ alkyl, in particular C₁-C₄        alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, in        particular C₂-C₄ alkenyl, or a substituted or unsubstituted        C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl, with r being 1, 2, 3        or 4, in particular r is 1,    -   with R^(c) being —CH₂OH, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH(CH₃)₂,        —CH₂CF₃, —CHFCF₃, —CF₂CF₃, —CHF₂, —CH₂F, —CF₃.

In some embodiments, R¹ comprises the general formula 2a to 2j,

-   -   with each T being selected independently from each other from        —CH₂, —NH, —S, —O, —CHCH₃, —C(CH₃)₂ or —NR^(c), in particular        from NH, —S or —O, and    -   with T′ being selected from —CH₂, —NH, —S, —O, —CHCH₃, —C(CH₃)₂        or —NR^(c), and    -   with each T″ being selected independently from each other from        being selected from —CH or ═N,    -   with R⁴ and R⁵ being selected independently from each other from        —H, —F, —CH₃, —CH₂CH₃, —OCH₃, —CH₂CF₃, —CHFCF₃, —CF₂CF₃, —CHF₂,        —CH₂F or —CF₃, in particular with R⁵ and R⁶ being selected        independently from each other from H, —F or —CH₃, and    -   with R⁶ being selected from —OH, —OCH₃, —OCH₂CH₃, —CH₃ or H,    -   with R⁷ being selected from ═NH, ═S or ═O, in particular from O,        and    -   with n of Z¹ _(n) being 0, 1, 2 or 3, in particular n of Z¹ _(n)        being 0 or 1, and with each Z¹ independently from any other Z¹        being selected from —F, —Cl, —Br, —I, CN, —R^(a), —OR^(a),        —(CH₂)_(r)OR^(a), —SR^(a), —(CH₂)_(r)SR^(a) or —NR^(a) ₂, with        each R^(a) being selected independently from each other from H,        a substituted or unsubstituted C₁-C₈ alkyl, in particular C₁-C₄        alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, in        particular C₂-C₄ alkenyl, or a substituted or unsubstituted        C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl, with r being 1, 2, 3        or 4, in particular r is 1,    -   with R^(c) being —CH₂OH, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH(CH₃)₂,        —CH₂CF₃, —CHFCF₃, —CF₂CF₃, —CHF₂, —CH₂F, —CF₃.

In some embodiments, R¹ comprises the general formula 2b′ to 2i′ or 2bto 2i, in particular the general formula 2b to 2i, with R^(c), n ofZ_(n) ¹ and Z_(n) ¹ having the same meaning as defined previously, and

-   -   with T′ of the compound according to formula 2a being selected        from —NH, —S, —O or —NR^(c), wherein in particular T′ is O, R⁴        and R⁵ being selected independently from each other from —H, —F,        —CH₃, in particular with R⁵ and R⁶ being H,    -   with T′ of the compound according to formula 2b or 2c being        selected from —NH, —S, —O or —NR^(c), wherein in particular T′        is S or —NH, and T″ being selected from —CH or ═N, and with R⁶        being selected from —CH₃ or H, in particular R⁶ is H,    -   with each T of the compound according to formula 2d being        selected independently from each other from —NH, —S, —O or        —NR^(c), in particular at least one T is selected from NH or        —NCH₃, more particularly the T in the position 4, with respect        to the connection to the parent moiety, is —NH, and with R⁷        being selected from ═NH, ═S or ═O, in particular from O, and    -   with T′ of the compound according to formula 2e being selected        from —CH₂, —NH, —S or —O, in particular T′ being —NH or —O,    -   with each T″ of the compound according to formula 2f being        selected independently from each other from —CH or ═N, in        particular each T″ is ═N,    -   with T′ of the compound according to formula 2g or 2h being        selected from —NH, —S, —O or —NR^(c), wherein in particular T′        is —NR^(c) or —NH, and T″ being selected from —CH or ═N, in        particular T″ is ═N,    -   with T′ of the compound according to formula 2i or 2j being        selected from —NH or —NR^(c), wherein in particular T′ is —NH,        and T″ is ═N.

In some embodiments, R¹ comprises the general formula 2b to 2h,

with T, T′, T″, n of Z_(n) ¹, Z_(n) ¹, R⁶ and R⁷ having the same meaningas defined previously.

In some embodiments, R¹ comprises the general formula 2b′ to 2h′ or 2bto 2h, in particular the general formula 2b to 2h, with R^(c), n ofZ_(n) ¹ and Z_(n) ¹ having the same meaning as defined previously, and

-   -   with T′ of the compound according to formula 2b or 2c being        selected from —NH, —S, —O or —NR^(c), wherein in particular T′        is S or —NH, and T″ being selected from —CH or ═N, and with R⁶        being selected from —CH₃ or H, in particular R⁶ is H,    -   with each T of the compound according to formula 2d being        selected independently from each other from —NH, —S, —O or        —NR^(c), in particular at least one T is selected from NH or        —NCH₃, more particularly the T in the position 4, with respect        to the connection to the parent moiety, is —NH, and with R⁷        being selected from ═NH, ═S or ═O, in particular from O, and    -   with T′ of the compound according to formula 2e being selected        from —CH₂, —NH, —S or —O, in particular T′ being —O,    -   with each T″ of the compound according to formula 2f being        selected independently from each other from —CH or ═N, in        particular each T″ is ═N,    -   with T′ of the compound according to formula 2g or 2h being        selected from —NH, —S, —O or —NR^(c), wherein in particular T′        is —NR^(c) or —NH, and T″ being selected from —CH or ═N, in        particular T″ is ═N.

In some embodiments, R¹ comprises the general formula 2b, 2c, 2e, 2g or2h

with T, T′, T″, n of Z_(n) ¹, Z_(n) ¹, R⁶ and R⁷ having the same meaningas defined previously.

In some embodiments, R¹ comprises the general formula 2b′, 2c′, 2e′, 2g′or 2h′ or 2b, 2c, 2e, 2g or 2h, in particular the general formula 2b,2c, 2e, 2g or 2h, with R^(c), n of Z_(n) and Z_(n) having the samemeaning as defined previously and

-   -   with T′ of the compound according to formula 2b or 2c being        selected from —NH, —S, —O or —NR^(c), wherein in particular T′        is S or —NH, and T″ being selected from —CH or ═N, and with R⁶        being selected from —CH₃ or H, in particular R⁶ is H,    -   with T′ of the compound according to formula 2e being selected        from —CH₂, —NH, —S or —O, in particular T′ being —O,    -   with T′ of the compound according to formula 2g or 2h being        selected from —NH, —S, —O or —NR^(c), wherein in particular T′        is —NR^(c) or —NH, and T″ being selected from —CH or ═N, in        particular T″ is ═N.

In some embodiments, R¹ comprises the general formula 2b, 2c, 2g or 2h,

with T, T′, T″, n of Z_(n) ¹, Z_(n) ¹, R⁶ and R⁷ having the same meaningas defined previously.

In some embodiments, R¹ comprises the general formula 2b′, 2c′, 2g′ or2h′ or 2b, 2c, 2g or 2h, in particular the general formula 2b, 2c, 2g or2h, with R^(c), n of Z_(n) ¹ and Z_(n) ¹ having the same meaning asdefined previously and

-   -   with T′ of the compound according to formula 2b or 2c being        selected from —NH, —S, —O or —NR^(c), wherein in particular T′        is S or —NH, and T″ being selected from —CH or ═N, and with R⁶        being selected from —CH₃ or H, in particular R⁶ is H,    -   with T′ of the compound according to formula 2g or 2h being        selected from —NH, —S, —O or —NR^(c), wherein in particular T′        is —NR^(c) or —NH, and T″ being selected from —CH or ═N, in        particular T″ is ═N.

In some embodiments, R¹ comprises the general formula 2b or 2c

with T′, T″, n of Z_(n) ¹, Z_(n) ¹ and R⁶ having the same meaning asdefined previously.

In some embodiments, R¹ comprises the general formula 2b′ or 2c′ or 2bor 2c, in particular the general formula 2b or 2c, with R^(c), n ofZ_(n) and Z_(n) having the same meaning as defined previously,

-   -   with T′ of the compound according to formula 2b or 2c being        selected from —NH, —S, —O or —NR^(c), wherein in particular T′        is S or —NH, and T″ being selected from —CH or ═N, and with R⁶        being selected from —CH₃ or H, in particular R⁶ is H.

In some embodiments, R¹ comprises the general formula 2c

with T′, T″, n of Z_(n) ¹, Z_(n) ¹ and R⁶ having the same meaning asdefined previously.

In some embodiments, R¹ comprises the general formula 2c′ or 2c, inparticular the general formula 2c, with R^(c), n of Z_(n) and Z_(n)having the same meaning as defined previously,

-   -   with T′ of the compound according to formula 2c being selected        from —NH, —S, —O or —NR^(c), wherein in particular T′ is —NH,        and T″ being selected from —CH or ═N, in particular from ═N, and        with R⁶ being selected from —CH₃ or H, in particular R⁶ is H.

In some embodiments, R^(c) is selected from —CH₂OH, —CH₃, —CH₂CH₃,—CH₂CH₂CH₃ or —CH(CH₃)₂, in particular from —CH₃, —CH₂CH₃ or —CH(CH₃)₂,more particularly R^(c) is CH₃.

In some embodiments, n of Z¹ _(n) is 0, 1 or 2, in particular n is 0 or1.

In some embodiments, n of Z¹ _(n) is 1.

In some embodiments, n of Z¹ _(n) is 0.

In some embodiments, each Z¹ independently from any other Z¹ is selectedfrom —F, —Cl, —Br, —I, CN, —R^(a), —OR^(a), CH₂OR^(a), with each R^(a)being selected independently from each other from H, a substituted orunsubstituted C₁-C₈ alkyl, in particular C₁-C₄ alkyl, a substituted orunsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or asubstituted or unsubstituted C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, each Z¹ independently from any other Z¹ is selectedfrom —F, —Cl, —Br, —I, CN, CH₂OR^(a) or —OR^(a), with each R^(a) beingselected independently from each other from H, a substituted orunsubstituted C₁-C₈ alkyl, in particular C₁-C₄ alkyl, a substituted orunsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or asubstituted or unsubstituted C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, each Z¹ independently from any other Z¹ is selectedfrom —F, —Cl, —Br, —I, CN, OH, CH₂OH, CH₂OR^(a) or —OR^(a) with R^(a)being selected from a C₁-C₄ alkyl, C₂-C₄ alkenyl or C₂-C₄ alkenyl, inparticular from a C₁-C₄ alkyl.

In some embodiments, each Z¹ independently from any other Z¹ is selectedfrom CN, OH, —OCH₃, —OCH₂CH₃, —O(CH₂)₂CH₃, —O(CH₂)CCH, —CH₂OCH₃,—CH₂OCH₂CH₃, —CH₂O(CH₂)₂CH₃ or —CH₂O(CH₂)CCH, in particular from CN, OH,—OCH₃ or —CH₂OCH₃, more particularly from —OCH₃ or —CH₂OCH₃.

In some embodiments, R¹ is selected from

or derivatives thereof.

In some embodiments, R¹ is selected from

or derivatives thereof.

In some embodiments, R¹ is selected from

or derivatives thereof.

In some embodiments, R¹ is selected from

or derivatives thereof.

In some embodiments, R¹ is selected from

or derivatives thereof.

In some embodiments R¹ comprises the general formula 3a to 3k

-   -   with each T being selected independently from each other from        —CH₂, —NH, —S, —O, —CHCH₃, —C(CH₃)₂ or —NR^(c), in particular        from NH, —S or —O, and    -   with T′ being selected from —CH₂, —NH, —S, —O, —CHCH₃, —C(CH₃)₂        or —NR^(c), and    -   with each T″ being selected independently from each other from        being selected from —CH or ═N,    -   with R⁴ and R⁵ being selected independently from each other from        —H, —F, —CH₃, —CH₂CH₃, —OCH₃, —CH₂CF₃, —CHFCF₃, —CF₂CF₃, —CHF₂,        —CH₂F or —CF₃, in particular with R⁵ and R⁶ being selected        independently from each other from H, —F or —CH₃, and    -   with R⁶ being selected from —OH, —OCH₃, —OCH₂CH₃, —CH₃ or H,    -   with R⁷ being selected from ═NH, ═S or ═O, in particular from O,        and    -   with R^(c) being —CH₂OH, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH(CH₃)₂,        —CH₂CF₃, —CHFCF₃, —CF₂CF₃, —CHF₂, —CH₂F, —CF₃.

In some embodiments R¹ comprises the general formula 3a to 3k

-   -   with T′ of the compound according to formula 3a being selected        from —NH, —S, —O or —NR^(c), wherein in particular T′ is O, R⁴        and R⁵ being selected independently from each other from —H, —F,        —CH₃, in particular with R⁵ and R⁶ being H,    -   with T′ of the compound according to formula 3b or 3c being        selected from —NH, —S, —O or —NR^(c), wherein in particular T′        is —NH, and T″ being selected from —CH or ═N, and with R⁶ being        selected from —CH₃ or H, in particular R⁶ is H,    -   with each T of the compound according to formula 3d being        selected independently from each other from —NH, —S, —O or        —NR^(c), in particular at least one T is selected from NH or        —NCH₃, more particularly the T in the position 4, with respect        to the connection to the parent moiety, is —NH, and with R⁷        being selected from ═NH, ═S or ═O, in particular from O, and    -   with T′ of the compound according to formula 3e being selected        from —CH₂, —NH, —S or —O, in particular T′ being —NH or —O,    -   with each T″ of the compound according to formula 3f being        selected independently from each other from —CH or ═N, in        particular each T″ is ═N,    -   with T′ of the compound according to formula 3g or 3h being        selected from —NH or —NR^(c), wherein in particular T′ is —NCH₃,        and T″ being selected from —CH or ═N, in particular from ═N,    -   with T′ of the compound according to formula 3i or 3j being        selected from —NH or —NR^(c), wherein in particular T′ is —NH,        and T″ is ═N.

In some embodiments R¹ is selected from a substituted or unsubstitutedC₅ heterocycle or a substituted or unsubstituted C₅-C₆ heteroaryl,wherein in particular the substituted C₅ heterocycle or the substitutedC₅-C₆ heteroaryl comprises at least one substituent Z¹

In some embodiments R¹ is selected from a substituted or unsubstitutedpyran, furan, imidazole, thiophen, pyrrol, pyridine, pyrazine, thiazol,oxazol, cumarin, benzoimidazole, indol, Isoindol, benzodiazol,benzotriazol, benzoxazol, benzothiazol or pyrazin and derivativesthereof, wherein in particular the substituted compounds comprises atleast one substituent Z¹.

In some embodiments, R^(c) is selected from —CH₂OH, —CH₃, —CH₂CH₃,—CH₂CH₂CH₃ or —CH(CH₃)₂, in particular from —CH₃, —CH₂CH₃ or —CH(CH₃)₂,more particularly R^(c) is CH₃.

In some embodiments, R² is selected from

-   -   a substituted or unsubstituted alkyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkyl,    -   a substituted or unsubstituted alkenyl, in particular a        substituted or unsubstituted C₂-C₁₂ alkenyl,    -   a substituted or unsubstituted alkynyl, in particular a        substituted or unsubstituted C₂-C₁₂ alkynyl,    -   a substituted or unsubstituted cycloalkyl, in particular a        substituted or unsubstituted C₃-C₁₀ cycloalkyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl.

In some embodiments, R² is selected from

-   -   a substituted or unsubstituted alkyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkyl,    -   a substituted or unsubstituted alkenyl, in particular a        substituted or unsubstituted C₂-C₁₂ alkenyl,    -   a substituted or unsubstituted alkynyl, in particular a        substituted or unsubstituted C₂-C₁₂ alkynyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl, or    -   a substituted or unsubstituted heteroaryl, in particular a        substituted or unsubstituted C₅-C₁₀ heteroaryl.

In some embodiments, R² is selected from

-   -   a substituted or unsubstituted C₁-C₄ alkyl,    -   a substituted or unsubstituted C₂-C₄ alkenyl,    -   a substituted or unsubstituted C₂-C₄ alkynyl,    -   a substituted or unsubstituted C₆ aryl, or    -   a substituted or unsubstituted C₅-C₆— heteroaryl.

In some embodiments, R² is selected from

-   -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula -L-Ar,        -   with L being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl,            -   an alkenyl, in particular a C₂-C₁₂ alkenyl, more                particularly a C₂-C₄ alkenyl,            -   an alkynyl, in particular a C₂-C₁₂ alkynyl, more                particularly a C₂-C₄ alkynyl, and            -   Ar being a substituted or unsubstituted C₅-C₆— aryl or a                substituted or unsubstituted C₅-C₆— heteroaryl, or    -   a substituted or unsubstituted C₆— aryl or a substituted or        unsubstituted C₅-C₆— heteroaryl, wherein in particular the        substituted C₆— aryl or the substituted C₅-C₆— heteroaryl        comprises at least one substituent Z².

In some embodiments, R² is selected from

-   -   a substituted alkyl, wherein the substituted alkyl comprises the        formula -L-Ar,        -   with L being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl, and            -   Ar being a substituted or unsubstituted C₅-C₆— aryl or a                substituted or unsubstituted C₅-C₆— heteroaryl, or    -   a substituted or unsubstituted C₆— aryl or a substituted or        unsubstituted C₅-C₆— heteroaryl wherein in particular the        substituted C₆— aryl or the substituted C₅-C₆— heteroaryl        comprises at least one substituent Z².

In some embodiments, R² is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula -L-Ar, with L being analkyl, in particular a C₁-C₂ alkyl, more particularly a C₁-C₄ alkyl, andAr being a substituted or unsubstituted C₅-C₆— aryl or a substituted orunsubstituted C₅-C₆— heteroaryl, wherein in particular the substitutedC₆— aryl or the substituted C₅-C₆— heteroaryl comprises at least onesubstituent Z².

In some embodiments, R² is selected from a substituted or unsubstitutedC₆— aryl or a substituted or unsubstituted C₅-C₆— heteroaryl, wherein inparticular the substituted C₆— aryl or the substituted C₅-C₆— heteroarylcomprises at least one substituent Z².

In some embodiments, R² is selected from

-   -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula 4a

or

-   -   a substituted or unsubstituted C₆— aryl, wherein the substituted        C₆ aryl comprises the formula 4b

-   -   with L being        -   an alkyl, in particular a C₁-C₁₂ alkyl, more particularly a            C₁-C₄ alkyl,        -   an alkenyl, in particular a C₂-C₁₂ alkenyl, more            particularly a C₂-C₄ alkenyl,        -   an alkynyl, in particular a C₂-C₁₂ alkynyl, more            particularly a C₂-C₄ alkynyl, and    -   o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3,        more particularly 0 or 1, and each Z² independently from any        other Z² is selected from —F, —Cl, —Br, —I, CN, —R^(b), —OR^(b),        —(CH₂)_(r)OR^(b), —SR^(b), —(CH₂)_(r)SR^(b) or —NR^(b) ₂, with        each R^(b) being selected independently from each other from H,        a substituted or unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄        alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, in        particular C₂-C₄ alkenyl, or a substituted or unsubstituted        C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1, 2,        3 or 4, in particular r is 1.

In some embodiments, R² is selected from

-   -   a substituted alkyl wherein the substituted alkyl comprises the        formula 4a

or

-   -   a substituted or unsubstituted C₆— aryl, wherein the substituted        C₆ aryl comprises the formula 4b

-   -   with L being an alkyl, in particular a C₁-C₁₂ alkyl, more        particularly a C₁-C₄ alkyl, and    -   o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3,        more particularly 0 or 1, and each Z² independently from any        other Z² is selected from —F, —Cl, —Br, —I, CN, —R^(b), —OR^(b),        —(CH₂)_(r)OR^(b), —SR^(b), —(CH₂)_(r)SR^(b) or —NR^(b) ₂, with        each R^(b) being selected independently from each other from H,        a substituted or unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄        alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, in        particular C₂-C₄ alkenyl, or a substituted or unsubstituted        C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1, 2,        3 or 4, in particular r is 1.

In some embodiments, R² is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 4a, with L being an alkyl,in particular a C₁-C₁₂ alkyl, more particularly a C₁-C₄ alkyl, and o ofZ² _(o) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, moreparticularly 0 or 1, and each Z² independently from any other Z² isselected from —F, —Cl, —Br, —I, CN, —R^(b), —OR^(b), —(CH₂)_(r)OR^(b) or—NR^(b) ₂, with each R^(b) being selected independently from each otherfrom H, a substituted or unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, in particularC₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, inparticular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in particular r is1.

In some embodiments, R² is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 4a, with L being an alkyl,in particular a C₁-C₁₂ alkyl, more particularly a C₁-C₄ alkyl, and o ofZ² _(o) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, moreparticularly 0 or 1, and each Z² independently from any other Z² isselected from —F, —Cl, —Br, —I, CN, —R^(b), —OR^(b), —(CH₂)_(r)OR^(b) or—NR^(b) ₂, with each R^(b) being selected independently from each otherfrom H, a substituted or unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, in particularC₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, inparticular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in particular r is1.

In some embodiments, R² is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 4a, with L being

-   -   an alkyl, in particular a C₁-C₁₂ alkyl, more particularly a        C₁-C₄ alkyl,    -   an alkenyl, in particular a C₂-C₁₂ alkenyl, more particularly a        C₂-C₄ alkenyl,    -   an alkynyl, in particular a C₂-C₁₂ alkynyl, more particularly a        C₂-C₄ alkynyl,        and o of Z² _(o) is 1 and Z² is selected from —F, —Cl, —Br, —I,        CN, —R^(b), —OR^(b), —(CH₂)_(r)OR^(b) or —NR^(b) ₂, with each        R^(b) being selected independently from each other from H, a        substituted or unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄        alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, in        particular C₂-C₄ alkenyl, or a substituted or unsubstituted        C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1, 2,        3 or 4, in particular r is 1.

In some embodiments, R² is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 4a, with L being an alkyl,in particular a C₁-C₁₂ alkyl, more particularly a C₁-C₄ alkyl, and o ofZ² _(o) is 0.

In some embodiments, R² is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 4b, with o of Z² _(o) being0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, more particularly 0 or1, and each Z² independently from any other Z² is selected from —F, —Cl,—Br, —I, CN, —R^(b), —OR^(b), —(CH₂)_(r)OR^(b) or —NR^(b) ₂, with eachR^(b) being selected independently from each other from H, a substitutedor unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substitutedor unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or asubstituted or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄alkynyl, with r being 1, 2, 3 or 4, in particular r is 1.

In some embodiments, R² is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 4b, with o of Z² _(o) being0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, more particularly 0 or1, and each Z² independently from any other Z² is selected from —F, —Cl,—Br, —I, CN, —R^(b), —OR^(b), —(CH₂)_(r)OR^(b) or —NR^(b) ₂, with eachR^(b) being selected independently from each other from H, a substitutedor unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substitutedor unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or asubstituted or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄alkynyl, with r being 1, 2, 3 or 4, in particular r is 1.

In some embodiments, R² is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 4b, with o of Z² _(o) being1 and Z² is selected from —F, —Cl, —Br, —I, CN, —R^(b), —OR^(b),—(CH₂)_(r)OR^(b) or —NR^(b) ₂, with each R^(b) being selectedindependently from each other from H, a substituted or unsubstitutedC₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted or unsubstitutedC₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted orunsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl, with r being1, 2, 3 or 4, in particular r is 1.

In some embodiments, R² is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 4b, with o of Z² _(o) being0.

In some embodiments, o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular0, 1, 2 or 3, more particularly 0 or 1, and each Z² is selectedindependently from any other Z² from —F, —Cl, —Br, —I, CN, —R^(b),—OR^(b), CH₂OR^(b) or —NR^(b) ₂, in particular from —F, —Cl, —R^(b),—OR^(b), CH₂OR^(b) or —NR^(b) ₂, more particularly from —F, —Cl, —R^(b),with each R^(b) being selected independently from each other from H, asubstituted or unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, asubstituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenylor a substituted or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄alkynyl.

In some embodiments, o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular0, 1, 2 or 3, more particularly 0 or 1, and each Z² is selectedindependently from any other Z² from —F, —Cl, —Br, —I or —R^(b), inparticular from R^(b), with R^(b) being selected from a substituted orunsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted orunsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl or asubstituted or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄alkynyl.

In some embodiments, o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular0, 1, 2 or 3, more particularly 0 or 1, and each Z² is selectedindependently from any other Z² from —F, —Cl, —Br, —I or —R^(b), inparticular from R^(b), with R^(b) being selected from a substituted orunsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl.

In some embodiments, o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular0, 1, 2 or 3, more particularly 0 or 1, and each Z² is selectedindependently from any other Z² is selected from —R^(b), with R^(b)being selected from a substituted or unsubstituted C₁-C₁₂ alkyl, inparticular C₁-C₄ alkyl.

In some embodiments, o of Z² _(o) is 0 or 1.

In some embodiments, o of Z² _(o) is 1.

In some embodiments, o of Z² _(o) is 0.

In some embodiments, R² is selected from

or derivatives thereof.

In some embodiments, R² is selected from

or derivatives thereof.

In some embodiments, R² is selected from

or derivatives thereof.

In some embodiments, R² is selected from

or derivatives thereof.

In some embodiments, R² is selected from

or derivatives thereof.

In some embodiments, R² is selected from

or derivatives thereof.

In some embodiments, R³ is selected from

-   -   a substituted or unsubstituted alkyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkyl,    -   a substituted or unsubstituted alkenyl, in particular a        substituted or unsubstituted C₂-C₁₂ alkenyl,    -   a substituted or unsubstituted alkynyl, in particular a        substituted or unsubstituted C₂-C₁₂ alkynyl,    -   a substituted or unsubstituted cycloalkyl, in particular a        substituted or unsubstituted C₃-C₁₀ cycloalkyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl.

In some embodiments, R³ is selected from

-   -   a substituted or unsubstituted alkyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkyl,    -   a substituted or unsubstituted alkenyl, in particular a        substituted or unsubstituted C₂-C₁₂ alkenyl,    -   a substituted or unsubstituted alkynyl, in particular a        substituted or unsubstituted C₂-C₁₂ alkynyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl, or    -   a substituted or unsubstituted heteroaryl, in particular a        substituted or unsubstituted C₅-C₁₀ heteroaryl.

In some embodiments, R³ is selected from

-   -   a substituted or unsubstituted C₁-C₄ alkyl,    -   a substituted or unsubstituted C₂-C₄ alkenyl,    -   a substituted or unsubstituted C₂-C₄ alkynyl,    -   a substituted or unsubstituted C₆ aryl, or    -   a substituted or unsubstituted C₅-C₆— heteroaryl.

In some embodiments, R³ is selected from

-   -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula -D-Ar,        -   with D being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl,            -   an alkenyl, in particular a C₂-C₁₂ alkenyl, more                particularly a C₂-C₄ alkenyl,            -   an alkynyl, in particular a C₂-C₁₂ alkynyl, more                particularly a C₂-C₄ alkynyl, and            -   Ar being a substituted or unsubstituted C₅-C₆— aryl or a                substituted or unsubstituted C₅-C₆— heteroaryl, or    -   a substituted or unsubstituted C₆— aryl or a substituted or        unsubstituted C₅-C₆— heteroaryl, wherein in particular the        substituted C₆— aryl or the substituted C₅-C₆— heteroaryl        comprises at least one substituent Z³.

In some embodiments, R³ is selected from

-   -   a substituted alkyl, wherein the substituted alkyl comprises the        formula -D-Ar,        -   with D being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl, and            -   Ar being a substituted or unsubstituted C₅-C₆— aryl or a                substituted or unsubstituted C₅-C₆— heteroaryl, or    -   a substituted or unsubstituted C₆— aryl or a substituted or        unsubstituted C₅-C₆— heteroaryl wherein in particular the        substituted C₆— aryl or the substituted C₅-C₆— heteroaryl        comprises at least one substituent Z³.

In some embodiments, R³ is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula -D-Ar, with L being analkyl, in particular a C₁-C₁₂ alkyl, more particularly a C₁-C₄ alkyl,and Ar being a substituted or unsubstituted C₅-C₆— aryl or a substitutedor unsubstituted C₅-C₆— heteroaryl, wherein in particular thesubstituted C₆— aryl or the substituted C₅-C₆— heteroaryl comprises atleast one substituent Z³.

In some embodiments, R³ is selected from a substituted or unsubstitutedC₆— aryl or a substituted or unsubstituted C₅-C₆— heteroaryl, wherein inparticular the substituted C₆— aryl or the substituted C₅-C₆— heteroarylcomprises at least one substituent Z³.

In some embodiments, R³ is selected from

-   -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula 5a

or

-   -   a substituted or unsubstituted C₆— aryl, wherein the substituted        C₆ aryl comprises the formula 5b

-   -   -   with D being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl,            -   an alkenyl, in particular a C₂-C₁₂ alkenyl, more                particularly a C₂-C₄ alkenyl,            -   an alkynyl, in particular a C₂-C₁₂ alkynyl, more                particularly a C₂-C₄ alkynyl, and        -   p of Z³ _(p) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or            3, more particularly 0 or 1, and        -   each Z³ independently from any other Z³ is selected from —F,            —Cl, —Br, —I, CN, —R^(d), —OR^(d), —(CH₂)_(r)OR^(d),            —SR^(d), —(CH₂)_(r)SR^(d) or —NR^(d) ₂, with each R^(d)            being selected independently from each other from H, a            substituted or unsubstituted C₁-C₁₂ alkyl, in particular            C₁-C₄ alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl,            in particular C₂-C₄ alkenyl, or a substituted or            unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl,            with r being 1, 2, 3 or 4, in particular r is 1.

In some embodiments, R³ is selected from

-   -   a substituted alkyl wherein the substituted alkyl comprises the        formula 5a

or

-   -   a substituted or unsubstituted C₆— aryl, wherein the substituted        C₆ aryl comprises the formula 5b

-   -   -   with D being an alkyl, in particular a C₁-C₁₂ alkyl, more            particularly a C₁-C₄ alkyl, and        -   p of Z³ _(p) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or            3, more particularly 0 or 1, and each Z³ independently from            any other Z³ is selected from —F, —Cl, —Br, —I, CN, —R^(d),            —OR^(d), —(CH₂)_(r)OR^(d), —SR^(d), —(CH₂)_(r)SR^(d) or            —NR^(d) ₂, with each R^(d) being selected independently from            each other from H, a substituted or unsubstituted C₁-C₁₂            alkyl, in particular C₁-C₄ alkyl, a substituted or            unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl,            or a substituted or unsubstituted C₂-C₁₂ alkynyl, in            particular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in            particular r is 1.

In some embodiments, R³ is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 5a, with D being an alkyl,in particular a C₁-C₁₂ alkyl, more particularly a C₁-C₄ alkyl, and p ofZ³ _(p) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, moreparticularly 0 or 1, and each Z³ independently from any other Z³ isselected from —F, —Cl, —Br, —I, CN, —R^(d), —OR^(d), —(CH₂)_(r)OR^(d),—SR^(d), —(CH₂)_(r)SR^(d) or —NR^(d) ₂, with each R^(d) being selectedindependently from each other from H, a substituted or unsubstitutedC₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted or unsubstitutedC₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted orunsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl, with r being1, 2, 3 or 4, in particular r is 1.

In some embodiments, R³ is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 5a, with D being an alkyl,in particular a C₁-C₁₂ alkyl, more particularly a C₁-C₄ alkyl, and p ofZ³ _(p) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, moreparticularly 0 or 1, and each Z³ independently from any other Z³ isselected from —F, —Cl, —Br, —I, CN, —R^(d), —OR^(d), —(CH₂)_(r)OR^(d),—SR^(d), —(CH₂)_(r)SR^(d) or —NR^(d) ₂, with each R^(d) being selectedindependently from each other from H, a substituted or unsubstitutedC₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted or unsubstitutedC₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted orunsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl, with r being1, 2, 3 or 4, in particular r is 1.

In some embodiments, R³ is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 5a, with D being

-   -   an alkyl, in particular a C₁-C₁₂ alkyl, more particularly a        C₁-C₄ alkyl,    -   an alkenyl, in particular a C₂-C₁₂ alkenyl, more particularly a        C₂-C₄ alkenyl,    -   an alkynyl, in particular a C₂-C₁₂ alkynyl, more particularly a        C₂-C₄ alkynyl,        and p of Z³ _(p) is 1 and Z³ is selected from —F, —Cl, —Br, —I,        CN, —R^(d), —OR^(d), —(CH₂)_(r)OR^(d), —SR^(d), —(CH₂)_(r)SR^(d)        or —NR^(d) ₂, with each R^(d) being selected independently from        each other from H, a substituted or unsubstituted C₁-C₁₂ alkyl,        in particular C₁-C₄ alkyl, a substituted or unsubstituted C₂-C₁₂        alkenyl, in particular C₂-C₄ alkenyl, or a substituted or        unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl, with        r being 1, 2, 3 or 4, in particular r is 1.

In some embodiments, R³ is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 5a, with D being an alkyl,in particular a C₁-C₁₂ alkyl, more particularly a C₁-C₄ alkyl, and p ofZ³ _(p) is 0.

In some embodiments, R³ is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 5b, with p of Z³ _(p) being0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, more particularly 0 or1, and each Z³ independently from any other Z³ is selected from —F, —Cl,—Br, —I, CN, —R^(d), —OR^(d), —(CH₂)_(r)OR^(d), —SR^(d),—(CH₂)_(r)SR^(d) or —NR^(d) ₂, with each R^(d) being selectedindependently from each other from H, a substituted or unsubstitutedC₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted or unsubstitutedC₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted orunsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl, with r being1, 2, 3 or 4, in particular r is 1.

In some embodiments, R³ is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 5b, with p of Z³ _(p) being0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, more particularly 0 or1, and each Z³ independently from any other Z³ is selected from —F, —Cl,—Br, —I, CN, —R^(d), —OR^(d), —(CH₂)_(r)OR^(d), —SR^(d),—(CH₂)_(r)SR^(d) or —NR^(d) ₂, with each R^(d) being selectedindependently from each other from H, a substituted or unsubstitutedC₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted or unsubstitutedC₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted orunsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl, with r being1, 2, 3 or 4, in particular r is 1.

In some embodiments, R³ is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 5b, with p of Z³ _(p) being1 and Z³ is selected from —F, —Cl, —Br, —I, CN, —R^(d), —OR^(d),—(CH₂)_(r)OR^(d), —SR^(d), —(CH₂)_(r)SR^(d) or —NR^(d) ₂, with eachR^(d) being selected independently from each other from H, a substitutedor unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substitutedor unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or asubstituted or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄alkynyl, with r being 1, 2, 3 or 4, in particular r is 1.

In some embodiments, R³ is selected from a substituted alkyl, whereinthe substituted alkyl comprises the formula 5b, p of Z³ _(p) being 0.

In some embodiments, p of Z³ _(p) is 0, 1, 2, 3, 4 or 5, in particular0, 1, 2 or 3, more particularly 0 or 1, and each Z³ is selectedindependently from any other Z³ from —F, —Cl, —Br, —I, CN, —R^(d),—OR^(d), CH₂OR^(d) or —NR^(d) ₂, in particular from —F, —Cl, —R^(d),—OR^(d), CH₂OR^(d) or —NR^(d) ₂, more particularly from —F, —Cl, —R^(d),with each R^(d) being selected independently from each other from H, asubstituted or unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, asubstituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenylor a substituted or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄alkynyl.

In some embodiments, p of Z³ _(p) is 0, 1, 2, 3, 4 or 5, in particular0, 1, 2 or 3, more particularly 0 or 1, and each Z³ is selectedindependently from any other Z³ from —F, —Cl, —Br, —I or —R^(d), inparticular from R^(d), with R^(d) being selected from a substituted orunsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted orunsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl or asubstituted or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄alkynyl.

In some embodiments, p of Z³ _(p) is 0, 1, 2, 3, 4 or 5, in particular0, 1, 2 or 3, more particularly 0 or 1, and each Z³ is selectedindependently from any other Z³ from —F, —Cl, —Br, —I or —R^(d), inparticular from R^(d), with R^(d) being selected from a substituted orunsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl.

In some embodiments, p of Z³ _(p) is 0, 1, 2, 3, 4 or 5, in particular0, 1, 2 or 3, more particularly 0 or 1, and each Z³ is selectedindependently from any other Z³ is selected from —R^(d), with R^(d)being selected from a substituted or unsubstituted C₁-C₁₂ alkyl, inparticular C₁-C₄ alkyl.

In some embodiments, p of Z³ _(p) is 0 or 1.

In some embodiments, p of Z³ _(p) is 1.

In some embodiments, p of Z³ _(p) is 0.

In some embodiments, R³ is selected from

or derivatives thereof.

In some embodiments, R³ is selected from

or derivatives thereof.

In some embodiments, R³ is selected from

or derivatives thereof.

In some embodiments, R³ is selected from

or derivatives thereof.

Any embodiment described for R² or R³ according to the first aspect ofthe invention may be combined with any embodiment described for R¹according to the first aspect of the invention.

In some embodiments of a first sub aspect of the first aspect, R¹comprises the general formula 2a′ or 2e′,

-   -   with D being a C₁ to C₄ alkyl,        -   or the general formula 2a or 2e,

-   -   with each T being selected independently from each other from        —CH₂, —NH, —S, —O, —CHCH₃, —C(CH₃)₂ or —NR^(c), in particular        from NH, —S or —O, with R^(c) being —CH₂OH, —CH₃, —CH₂CH₃,        —CH₂CH₂CH₃, —CH(CH₃)₂, —CH₂CF₃, —CHFCF₃, —CF₂CF₃, —CHF₂, —CH₂F,        —CF₃ and    -   with T′ being selected from —CH₂, —NH, —S, —O, —CHCH₃, or        —C(CH₃)₂ and    -   with R⁴ and R⁵ being selected independently from each other from        —H, —F, —CH₃, —CH₂CH₃, —OCH₃, —CH₂CF₃, —CHFCF₃, —CF₂CF₃, —CHF₂,        —CH₂F or —CF₃, in particular with R⁵ and R⁶ being selected        independently from each other from H, —F or —CH₃, and    -   with n of Z¹ _(n) being 0, 1, 2 or 3, in particular n of Z¹ _(n)        being 0 or 1, and with each Z¹ independently from any other Z¹        being selected from —F, —Cl, —Br, —I, CN, —R^(a), —OR^(a),        —(CH₂)_(r)OR^(a), —SR^(a), —(CH₂)_(r)SR^(a) or —NR^(a) ₂, with        each R^(a) being selected independently from each other from H,        a substituted or unsubstituted C₁-C₈ alkyl, in particular C₁-C₄        alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, in        particular C₂-C₄ alkenyl, or a substituted or unsubstituted        C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl, with r being 1, 2, 3        or 4, in particular r is 1,    -   R² is selected from        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted saturated heterocycle, in            particular a substituted or unsubstituted C₃-C₁₀            heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₀₁ heteroaryl, and    -   and R³ is selected from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted saturated heterocycle, in            particular a substituted or unsubstituted C₃-C₁₀            heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl.

In some embodiments, particularly of the first sub aspect, R¹ comprisesthe general formula 2a or 2e,

in particular 2e, with D, T, T′, n of Z_(n) ¹, Z_(n) ¹, R⁴ and R⁵ havingthe same meaning as defined previously.

In some embodiments, particularly of the first sub aspect, T of thecompound according to formula 2a is selected from —NH, —S, —O or—NR^(c), wherein in particular T is O, R⁴ and R⁵ being selectedindependently from each other from —H, —F, —CH₃, in particular with R⁵and R⁶ being H, and T′ of the compound according to formula 2e isselected from —CH₂, —NH, —S or —O, in particular T′ is —NH or —O, moreparticularly O.

In some embodiments, particularly of the first sub aspect, n of Z¹ _(n)is 0, 1 or 2, in particular n is 0 or 1. In some embodiments, n of Z¹_(n) is 1. In some embodiments, n of Z¹ _(n) is 0.

In some embodiments, particularly of the first sub aspect, each Z¹independently from any other Z¹ is selected from —F, —Cl, —Br, —I, CN,—R^(a), —OR^(a), CH₂OR^(a), with each R^(a) being selected independentlyfrom each other from H, a substituted or unsubstituted C₁-C₈ alkyl, inparticular C₁-C₄ alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, inparticular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₈alkynyl, in particular C₂-C₄ alkynyl

In some embodiments, particularly of the first sub aspect, each Z¹independently from any other Z¹ is selected from —F, —Cl, —Br, —I, CN,CH₂OR^(a) or —OR^(a), with each R^(a) being selected independently fromeach other from H, a substituted or unsubstituted C₁-C₈ alkyl, inparticular C₁-C₄ alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, inparticular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₈alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, particularly of the first sub aspect, each Z¹independently from any other Z¹ is selected from —F, —Cl, —Br, —I, CN,OH, CH₂OH, CH₂OR^(a) or —OR^(a) with R^(a) being selected from a C₁-C₄alkyl, C₂-C₄ alkenyl or C₂-C₄ alkenyl, in particular from a C₁-C₄ alkyl.

In some embodiments, particularly of the first sub aspect, each Z¹independently from any other Z¹ is selected from CN, OH, —OCH₃,—OCH₂CH₃, —O(CH₂)₂CH₃, —O(CH₂)CCH, —CH₂OCH₃, —CH₂OCH₂CH₃, —CH₂O(CH₂)₂CH₃or —CH₂O(CH₂)CCH, in particular from CN, OH, —OCH₃ or —CH₂OCH₃, moreparticularly from —OCH₃ or —CH₂OCH₃.

In some embodiments, particularly of the first sub aspect, R² isselected from a substituted or unsubstituted C₃-C₆ cycloalkyl, asubstituted or unsubstituted C₆ aryl, or a substituted or unsubstitutedC₅-C₆— heteroaryl.

In some embodiments, particularly of the first sub aspect, R² isselected from

-   -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula -L-Ar,        -   with L being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl,            -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more                particularly a C₁-C₄ alkenyl,            -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more                particularly a C₁-C₄ alkynyl, and            -   Ar being a substituted or unsubstituted C₅-C₆— aryl or a                substituted or unsubstituted C₅-C₆— heteroaryl, or    -   a substituted or unsubstituted C₆— aryl or a substituted or        unsubstituted C₅-C₆-heteroaryl, wherein in particular the        substituted C₆— aryl or the substituted C₅-C₆-heteroaryl        comprises at least one substituent Z².

In some embodiments, particularly of the first sub aspect, R² isselected from

-   -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula 4a

or

-   -   a substituted or unsubstituted C₆— aryl, wherein the substituted        C₆ aryl comprises the formula 4b

-   -   -   with L being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl,            -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more                particularly a C₁-C₄ alkenyl,            -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more                particularly a C₁-C₄ alkynyl, and        -   o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or            3, more particularly 0 or 1, and            each Z² independently from any other Z² is selected from —F,            —Cl, —Br, —I, CN, —R^(b), —OR^(b), —(CH₂)_(r)OR^(b),            —SR^(b), —(CH₂)_(r)SR^(b) or —NR^(b) ₂, with each R^(b)            being selected independently from each other from H, a            substituted or unsubstituted C₁-C₁₂ alkyl, in particular            C₁-C₄ alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl,            in particular C₂-C₄ alkenyl, or a substituted or            unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl,            with r being 1, 2, 3 or 4, in particular r is 1.

In some embodiments, particularly of the first sub aspect, o of Z² _(o)is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, more particularly 0or 1, and each Z² is selected independently from any other Z² from —F,—Cl, —Br, —I, CN, —R^(b), —OR^(b), CH₂OR^(b) or —NR^(b) ₂, in particularfrom —F, —Cl, —R^(b), —OR^(b), CH₂OR^(b) or —NR^(b) ₂, more particularlyfrom —F, —Cl, —R^(b), with each R^(b) being selected independently fromeach other from H, a substituted or unsubstituted C₁-C₁₂ alkyl, inparticular C₁-C₄ alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl,in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₁₂alkynyl, in particular C₂-C₄ alkynyl,

In some embodiments, particularly of the first sub aspect, o of Z² _(o)is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, more particularly 0or 1, and each Z² is selected independently from any other Z² from —F,—Cl, —Br, —I or —R^(b), in particular from R^(b), with R^(b) beingselected from a substituted or unsubstituted C₁-C₁₂ alkyl, in particularC₁-C₄ alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, inparticular C₂-C₄ alkenyl or a substituted or unsubstituted C₂-C₁₂alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, particularly of the first sub aspect, o of Z² _(o)is 0

In some embodiments, particularly of the first sub aspect, R³ isselected from a substituted or unsubstituted alkyl, in particular asubstituted or unsubstituted C₁-C₁₀ alkyl, a substituted orunsubstituted alkenyl, in particular a substituted or unsubstitutedC₁-C₁₀ alkenyl, a substituted or unsubstituted alkynyl, in particular asubstituted or unsubstituted C₁-C₁₀ alkynyl, a substituted orunsubstituted cycloalkyl, in particular a substituted or unsubstitutedC₃-C₁₀ cycloalkyl, a substituted or unsubstituted aryl, in particular asubstituted or unsubstituted C₆-C₁₀ aryl, a substituted or unsubstitutedheteroaryl, in particular a substituted or unsubstituted C₅-C₁₀heteroaryl.

In some embodiments, particularly of the first sub aspect, R³ isselected from a substituted or unsubstituted alkyl, in particular asubstituted or unsubstituted C₁-C₁₀ alkyl, a substituted orunsubstituted alkenyl, in particular a substituted or unsubstitutedC₁-C₁₀ alkenyl, a substituted or unsubstituted alkynyl, in particular asubstituted or unsubstituted C₁-C₁₀ alkynyl, a substituted orunsubstituted aryl, in particular a substituted or unsubstituted C₆-C₁₀aryl, or a substituted or unsubstituted heteroaryl, in particular asubstituted or unsubstituted C₅-C₁₀ heteroaryl.

In some embodiments, particularly of the first sub aspect, R³ isselected from a substituted or unsubstituted C₁-C₄ alkyl, a substitutedor unsubstituted C₁-C₄ alkenyl, a substituted or unsubstituted C₁-C₄alkynyl, a substituted or unsubstituted C₆ aryl, a substituted orunsubstituted C₆-cycloalkyl; or a substituted or unsubstituted C₅-C₆—heteroaryl, in particular a substituted or unsubstituted C₆-cycloalkylor a substituted or unsubstituted C₅-C₆— heteroaryl.

In some embodiments, particularly of the first sub aspect, R³ isselected from

-   -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula -D-Ar,        -   with D being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl,            -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more                particularly a C₁-C₄ alkenyl,            -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more                particularly a C₁-C₄ alkynyl, and            -   Ar being a substituted or unsubstituted C₅-C₆— aryl or a                substituted or unsubstituted C₅-C₆— heteroaryl, or    -   a substituted or unsubstituted C₆— aryl or a substituted or        unsubstituted C₅-C₆-heteroaryl, wherein in particular the        substituted C₆— aryl or the substituted C₅-C₆-heteroaryl        comprises at least one substituent Z³.

In some embodiments, particularly of the first sub aspect, R³ isselected from

-   -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula 5a

or

-   -   a substituted or unsubstituted C₆— aryl, wherein the substituted        C₆ aryl comprises the formula 5b

in particular the formula 5b,

-   -   with D being        -   an alkyl, in particular a C₁-C₁₂ alkyl, more particularly a            C₁-C₄ alkyl,        -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more            particularly a C₁-C₄ alkenyl,        -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more            particularly a C₁-C₄ alkynyl, and    -   p of Z³ _(p) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3,        more particularly 0 or 1, and    -   each Z³ independently from any other Z³ is selected from —F,        —Cl, —Br, —I, CN, —R^(d), —OR^(d), —(CH₂)_(r)OR^(d)—SR^(d),        —(CH₂)_(r)SR^(d) or —NR^(d) ₂, with each R^(d) being selected        independently from each other from H, a substituted or        unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a        substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄        alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, in        particular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in        particular r is 1.

In some embodiments, particularly of the first sub aspect, p of Z³ _(p)is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, more particularly 0or 1, and each Z³ is selected independently from any other Z³ from —F,—Cl, —Br, —I, CN, —R^(d), —OR^(d), CH₂OR^(d) or —NR^(d) ₂, in particularfrom —F, —Cl, —R^(d), —OR^(d), CH₂OR^(d) or —NR^(d) ₂, more particularlyfrom —F, —Cl, —R^(d), with each R^(d) being selected independently fromeach other from H, a substituted or unsubstituted C₁-C₂ alkyl, inparticular C₁-C₄ alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl,in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₁₂alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, particularly of the first sub aspect, p of Z³ _(p)is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, more particularly 0or 1, and each Z³ is selected independently from any other Z³ from —F,—Cl, —Br, —I or —R^(d), in particular from R^(d), with R^(d) beingselected from a substituted or unsubstituted C₁-C₂ alkyl, in particularC₁-C₄ alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, inparticular C₂-C₄ alkenyl or a substituted or unsubstituted C₂-C₁₂alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, particularly of the first sub aspect, p of Z³ _(p)is 0.

In some embodiments, particularly of the first sub aspect, R¹ comprisesthe general formula 2e,

with T′ being O and n of Z_(n) ¹ being 0, andR³ is selected from a substituted or unsubstituted cycloalkyl, inparticular a substituted or unsubstituted C₃-C₁₀ cycloalkyl, moreparticularly cyclohexane Z_(n) ¹, R⁴ and R⁵ having the same meaning asdefined previously, andR² is selected from

-   -   a substituted or unsubstituted cycloalkyl, in particular a        substituted or unsubstituted C₃-C₁₀ cycloalkyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl,    -   a substituted or unsubstituted saturated heterocycle, in        particular a substituted or unsubstituted C₃-C₁₀ heterocycle, or    -   a substituted or unsubstituted heteroaryl, in particular a        substituted or unsubstituted C₅-C₁₀ heteroaryl, or        R² is selected from    -   a substituted or unsubstituted C₃-C₆ cycloalkyl, a substituted        or unsubstituted C₆ aryl, or a substituted or unsubstituted        C₅-C₆— heteroaryl, or        R² is selected from    -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula -L-Ar,        -   with L being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl,            -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more                particularly a C₁-C₄ alkenyl,            -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more                particularly a C₁-C₄ alkynyl, and            -   Ar being a substituted or unsubstituted C₅-C₆— aryl or a                substituted or unsubstituted C₅-C₆— heteroaryl, or            -   a substituted or unsubstituted C₆— aryl or a substituted                or unsubstituted C₅-C₆— heteroaryl, wherein in                particular the substituted C₆— aryl or the substituted                C₅-C₆— heteroaryl comprises at least one substituent Z²,                or                R² is selected from    -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula 4a

or

-   -   a substituted or unsubstituted C₆— aryl, wherein the substituted        C₆ aryl comprises the formula 4b

-   -   -   with L being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl,            -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more                particularly a C₁-C₄ alkenyl,            -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more                particularly a C₁-C₄ alkynyl, and        -   o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or            3, more particularly 0 or 1, and            -   each Z² independently from any other Z² is selected from                —F, —Cl, —Br, —I, CN, —R^(b), —OR^(b), —(CH₂)_(r)OR^(b),                —SR^(b), —(CH₂)_(r)SR^(b) or —NR^(b) ₂, with each R^(b)                being selected independently from each other from H, a                substituted or unsubstituted C₁-C₁₂ alkyl, in particular                C₁-C₄ alkyl, a substituted or unsubstituted C₂-C₁₂                alkenyl, in particular C₂-C₄ alkenyl, or a substituted                or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄                alkynyl, with r being 1, 2, 3 or 4, in particular r is                1, or            -   o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular 0, 1,                2 or 3, more particularly 0 or 1, and each Z² is                selected independently from any other Z² from —F, —Cl,                —Br, —I, CN, —R^(b), —OR^(b), CH₂OR^(b) or —NR^(b) ₂, in                particular from —F, —Cl, —R^(b), —OR^(b), CH₂OR^(b) or                —NR^(b) ₂, more particularly from —F, —Cl, —R^(b), with                each R^(b) being selected independently from each other                from H, a substituted or unsubstituted C₁-C₁₂ alkyl, in                particular C₁-C₄ alkyl, a substituted or unsubstituted                C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a                substituted or unsubstituted C₂-C₁₂ alkynyl, in                particular C₂-C₄ alkynyl, or            -   o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular 0, 1,                2 or 3, more particularly 0 or 1, and each Z² is                selected independently from any other Z² from —F, —Cl,                —Br, —I or —R^(b), in particular from R^(b), with R^(b)                being selected from a substituted or unsubstituted                C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted                or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄                alkenyl or a substituted or unsubstituted C₂-C₁₂                alkynyl, in particular C₂-C₄ alkynyl,            -   o of Z² _(o) is 0, or                R² is selected from

wherein the structure is exploratory and OH is in ortho, para or metaposition to the attachment position to the parent moiety,

wherein the structure is exploratory and OCH₃ is in ortho, para or metaposition to the attachment position to the parent moiety,

wherein the structure is exploratory and N is in ortho, para or metaposition to the attachment position to the parent moiety,

Particular embodiments of the first sub aspect are:

ETI-T-compound IUPAC name 24_Q_B(2Z,5Z)-2-(4-methoxybenzylimino)-3-(4-fluorophenyl)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_Q_I(2Z,5Z)-2-(4-methoxybenzylimino)-3-cyclohexyl-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_P_L(2Z,5Z)-2-(4-fluorobenzylimino)-3-(4-chlorophenyl)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_Q_L(2Z,5Z)-2-(4-methoxybenzylimino)-3-(4-chlorophenyl)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_P_I(2Z,5Z)-2-(4-fluorobenzylimino)-3-cyclohexyl-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_Q_X(2Z,5Z)-2-(4-methoxybenzylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-isobutylthiazolidin-4-one 24_A_B(2Z,5Z)-5-(2,3-dihydro-1,4-benzodioxin-6-ylmethylene)-3-(4-fluorophenyl)-2-(p-tolylimino)thiazolidin-4-one 24_B_I(2Z,5Z)-2-(4-fluorophenylimino)-3-cyclohexyl-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_B_X(2Z,5Z)-2-(4-fluorophenylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-isobutylthiazolidin-4-one 24_Q_A(2Z,5Z)-2-(4-methoxybenzylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-p-tolylthiazolidin-4-one 24_B_B(2Z,5Z)-2-(4-fluorophenylimino)-3-(4-fluorophenyl)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_C_N(2Z,5Z)-2-(benzylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-phenylthiazolidin-4-one 24_N_X(2Z,5Z)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-isobutyl-2-(phenylimino)thiazolidin-4-one 24_B_A(2Z,5Z)-2-(4-fluorophenylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-p-tolylthiazolidin-4-one 24_P_A(2Z,5Z)-2-(4-fluorobenzylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-p-tolylthiazolidin-4-one 24_A_A(2Z,5Z)-2-(p-tolylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-p-tolylthiazolidin-4-one 24_A_I(2Z,5Z)-3-cyclohexyl-5-(2,3-dihydro-1,4-benzodioxin-6-ylmethylene)-2-(p-tolylimino)thiazolidin-4-one 24_N_A(2Z,5Z)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-2-(phenylimino)-3-p-tolylthiazolidin-4-one 24_Q_N(2Z,5Z)-2-(4-methoxybenzylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-7-yl)methylene)-3-phenylthiazolidin-4-one 24_B_N(2Z,5Z)-2-(4-fluorophenylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-phenylthiazolidin-4-one 24_N_I(2Z,5Z)-3-cyclohexyl-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-2-(phenylimino)thiazolidin-4-one 24_P_X(2Z,5Z)-2-(4-fluorobenzylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-isobutylthiazolidin-4-one 24_P_N(2Z,5Z)-2-(4-fluorobenzylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-phenylthiazolidin-4-one 24_A_L(2Z,5Z)-2-(p-tolylimino)-3-(4-chlorophenyl)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_B_L(2Z,5Z)-2-(4-fluorophenylimino)-3-(4-chlorophenyl)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_N_B(2Z,5Z)-3-(4-fluorophenyl)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-2-(phenylimino)thiazolidin-4-one 24_A_X(2Z,5Z)-2-(p-tolylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-isobutylthiazolidin-4-one 24(2Z,5Z)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 24_F_N(2Z,5Z)-2-(4-methoxyphenylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-phenylthiazolidin-4-one 24_P_B(2Z,5Z)-2-(4-fluorobenzylimino)-3-(4-fluorophenyl)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_S_N(2Z,5Z)-2-((pyridin-3-yl)methylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-7-yl)methylene)-3-phenylthiazolidin-4-one24_A_N (2Z,5Z)-2-(p-tolylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-3-phenylthiazolidin-4-one 24_K_N(2Z,5Z)-2-(3-phenylpropylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-7-yl)methylene)-3-phenylthiazolidin-4-one 24_C_G(2Z,5Z)-2-(benzylimino)-3-butyl-5-((2,3-dihydrobenzo[b][1,4]dioxin-7-yl)methylene)thiazolidin-4-one 24_C_O(2Z,5Z)-2-(benzylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-7-yl)methylene)-3-phenethylthiazolidin-4-one 25(2Z,5Z)-5-((benzo[d][1,3]dioxol-5-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 24_C_B(2Z,5Z)-2-(benzylimino)-3-(4-fluorophenyl)-5-((2,3-dihydrobenzo[b][1,4]dioxin-7-yl)methylene)thiazolidin-4-one 24_A_V(2Z,5Z)-2-(p-tolylimino)-3-dodecyl-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_C_K(2Z,5Z)-2-(benzylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-7-yl)methylene)-3-(3-phenylpropyl)thiazolidin-4-one 24_B_V(2Z,5Z)-2-(4-fluorophenylimino)-3-dodecyl-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)thiazolidin-4-one 24_C_C(2Z,5Z)-3-benzyl-2-(benzylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-7-yl)methylene)thiazolidin-4-one 24_C_F(2Z,5Z)-2-(benzylimino)-5-((2,3-dihydrobenzo[b][1,4]dioxin-7-yl)methylene)-3-(4-methoxyphenyl)thiazolidin-4-one 24_U_N(2Z,5Z)-5-((2,3-dihydrobenzo[b][1,4]dioxin-7-yl)methylene)-2-(phenethylimino)-3-phenylthiazolidin-4-one

Any embodiment described for R² or R³ according to the first aspect ofthe invention may be combined with any embodiment described for R¹according to the first sub aspect of first aspect of the invention.

In some embodiments of a second sub aspect of the first aspect, R¹ isselected from

-   -   a substituted alkyl, in particular a substituted alky, alkenyl        or alkynyl, wherein the substituted alkyl, alkenyl or alkynyl        comprises the formula 6a

or

-   -   a substituted or unsubstituted heterocycle, in particular a        substituted or unsubstituted C₃-C₁₀ heterocycle, or    -   a substituted or unsubstituted heteroaryl, in particular a        substituted or unsubstituted C₅-C₁₀ heteroaryl,    -   a substituted or unsubstituted C₆— aryl, wherein the substituted        C₆ aryl comprises the formula 6b

-   -   with M being        -   an alkyl, in particular a C₁-C₁₂ alkyl, more particularly a            C₁-C₄ alkyl,        -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more            particularly a C₁-C₄ alkenyl,        -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more            particularly a C₁-C₄ alkynyl, and    -   l of Z¹⁰ _(l) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3,        more particularly 0 or 1, and    -   each Z¹⁰ independently from any other Z¹⁰ is selected from —F,        —Cl, —Br, —I, CN, —R^(e), —OR^(e), —(CH₂)_(r)OR^(e), —SR^(e),        —(CH₂)_(r)SR^(e) or —NR^(e) ₂, with each R^(e) being selected        independently from each other from H, a substituted or        unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a        substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄        alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, in        particular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in        particular r is 1.    -   and        R² is selected from    -   a substituted or unsubstituted alkyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkyl,    -   a substituted or unsubstituted alkoxy, in particular a        substituted or unsubstituted C₁-C₁₂ alkoxy,    -   a substituted or unsubstituted alkenyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkenyl,    -   a substituted or unsubstituted alkynyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkynyl,    -   a substituted or unsubstituted cycloalkyl, in particular a        substituted or unsubstituted C₃-C₁₀ cycloalkyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl,    -   a substituted or unsubstituted saturated heterocycle, in        particular a substituted or unsubstituted C₃-C₁₀ heterocycle, or    -   a substituted or unsubstituted heteroaryl, in particular a        substituted or unsubstituted C₅-C₁₀ heteroaryl, and        R³ is selected from a substituted or unsubstituted cycloalkyl,        in particular a substituted or unsubstituted C₃-C₁₀ cycloalkyl,        more particularly cyclohexane

Concerning embodiments of R₁ with respect to a substituted orunsubstituted heterocycle, in particular a substituted or unsubstitutedC₃-C₁₀ heterocycle, or a substituted or unsubstituted heteroaryl, inparticular a substituted or unsubstituted C₅-C₁₀ heteroaryl, referenceis made to the specific embodiments of the first aspect and the firstand third sub aspect of the invention.

In some embodiments, particularly of the second sub aspect, R¹ isselected from

-   -   a substituted or unsubstituted C₆— aryl, wherein the C₆ aryl        comprises the formula 6b

-   -   with M being an alkyl, in particular a C₁-C₁₂ alkyl, more        particularly a C₁-C₄ alkyl, and    -   l of Z¹⁰ _(l) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3,        more particularly 0 or 1, and        each Z¹⁰ independently from any other Z¹⁰ is selected from —F,        —Cl, —Br, —I, CN, —R^(e), —OR^(e), (CH₂)_(r)OR^(e), —SR^(e),        —(CH₂)_(r)SR^(e) or —NR^(e) ₂, with each R^(e) being selected        independently from each other from H, a substituted or        unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a        substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄        alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, in        particular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in        particular r is 1.

In some embodiments, particularly of the second sub aspect, l of Z¹⁰_(l) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, moreparticularly 0 or 1, and each Z¹⁰ is selected independently from anyother Z¹⁰ from —F, —Cl, —Br, —I, CN, —R^(e), —SR^(e), —CH₂SR^(e),—OR^(e), CH₂OR^(e) or —NR^(e) ₂, in particular from —F, —Cl, CN, —R^(e),—OR^(e), —CH₂OR^(e) or —NR^(e) ₂, more particularly from CN, —OR^(e) orCH₂OR^(e), with each R^(e) being selected independently from each otherfrom H, a substituted or unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, in particularC₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, inparticular C₂-C₄ alkynyl.

In some embodiments, particularly of the second sub aspect, l of Z¹⁰_(l) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3, moreparticularly 0 or 1, and each Z³ is selected independently from anyother Z³ from —F, —Cl, —Br, —I, CN, —OR^(e) or —CH₂OR^(e), in particularfrom R^(e), with R^(e) being selected from a substituted orunsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted orunsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl or asubstituted or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄alkynyl.

In some embodiments, particularly of the second sub aspect, l of Z¹⁰_(l) is 0, 1 or 2, in particular 0 or 1.

In some embodiments, particularly of the second sub aspect, R¹ isselected from.

In some embodiments, particularly of the second sub aspect, R² isselected from a substituted or unsubstituted alkyl, in particular asubstituted or unsubstituted C₁-C₁₀ alkyl, a substituted orunsubstituted alkenyl, in particular a substituted or unsubstitutedC₁-C₁₀ alkenyl, a substituted or unsubstituted alkynyl, in particular asubstituted or unsubstituted C₁-C₁₀ alkynyl, a substituted orunsubstituted cycloalkyl, in particular a substituted or unsubstitutedC₃-C₁₀ cycloalkyl, a substituted or unsubstituted aryl, in particular asubstituted or unsubstituted C₆-C₁₀ aryl, a substituted or unsubstitutedheteroaryl, in particular a substituted or unsubstituted C₅-C₁₀heteroaryl.

In some embodiments, particularly of the second sub aspect, R² isselected from a substituted or unsubstituted alkyl, in particular asubstituted or unsubstituted C₁-C₁₀ alkyl, a substituted orunsubstituted alkenyl, in particular a substituted or unsubstitutedC₁-C₁₀ alkenyl, a substituted or unsubstituted alkynyl, in particular asubstituted or unsubstituted C₁-C₁₀ alkynyl, a substituted orunsubstituted aryl, in particular a substituted or unsubstituted C₆-C₁₀aryl, or a substituted or unsubstituted heteroaryl, in particular asubstituted or unsubstituted C₅-C₁₀ heteroaryl.

In some embodiments, particularly of the second sub aspect, R² isselected from a substituted or unsubstituted C₁-C₄ alkyl, a substitutedor unsubstituted C₁-C₄ alkenyl, a substituted or unsubstituted C₁-C₄alkynyl, a substituted or unsubstituted C₆ aryl, or a substituted orunsubstituted C₅-C₆— heteroaryl.

In some embodiments, particularly of the second sub aspect, R¹ comprisesthe general formula 2e,

with T′ being O and n of Z_(n) ¹ being 0, andR³ is selected from a substituted or unsubstituted cycloalkyl, inparticular a substituted or unsubstituted C₃-C₁₀ cycloalkyl, moreparticularly cyclohexane Z_(n) ¹, R⁴ and R⁵ having the same meaning asdefined previously, andR² is selected from

-   -   a substituted or unsubstituted alkyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkyl,    -   a substituted or unsubstituted alkoxy, in particular a        substituted or unsubstituted C₁-C₁₂ alkoxy,    -   a substituted or unsubstituted alkenyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkenyl,    -   a substituted or unsubstituted alkynyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkynyl,    -   a substituted or unsubstituted cycloalkyl, in particular a        substituted or unsubstituted C₃-C₁₀ cycloalkyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl,    -   a substituted or unsubstituted saturated heterocycle, in        particular a substituted or unsubstituted C₃-C₁₀ heterocycle, or    -   a substituted or unsubstituted heteroaryl, in particular a        substituted or unsubstituted C₅-C₀₁ heteroaryl, or        R² is selected from    -   a substituted or unsubstituted cycloalkyl, in particular a        substituted or unsubstituted C₃-C₁₀ cycloalkyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl,    -   a substituted or unsubstituted saturated heterocycle, in        particular a substituted or unsubstituted C₃-C₁₀ heterocycle, or    -   a substituted or unsubstituted heteroaryl, in particular a        substituted or unsubstituted C₅-C₁₀ heteroaryl, or        R² is selected from    -   a substituted or unsubstituted C₃-C₆ cycloalkyl, a substituted        or unsubstituted C₆ aryl, or a substituted or unsubstituted        C₅-C₆— heteroaryl, or        R² is selected from    -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula -L-Ar,        -   with L being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl,            -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more                particularly a C₁-C₄ alkenyl,            -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more                particularly a C₁-C₄ alkynyl, and            -   Ar being a substituted or unsubstituted C₅-C₆— aryl or a                substituted or unsubstituted C₅-C₆— heteroaryl, or            -   a substituted or unsubstituted C₆— aryl or a substituted                or unsubstituted C₅-C₆— heteroaryl, wherein in                particular the substituted C₆— aryl or the substituted                C₅-C₆— heteroaryl comprises at least one substituent Z²,                or                R² is selected from    -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula 4a

or

-   -   a substituted or unsubstituted C₆— aryl, wherein the substituted        C₆ aryl comprises the formula 4b

-   -   -   with L being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl,            -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more                particularly a C₁-C₄ alkenyl,            -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more                particularly a C₁-C₄ alkynyl, and        -   o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or            3, more particularly 0 or 1, and            -   each Z² independently from any other Z² is selected from                —F, —Cl, —Br, —I, CN, —R^(b), —OR^(b), —(CH₂)_(r)OR^(b),                —SR^(b), —(CH₂)_(r)SR^(b) or —NR^(b) ₂, with each R^(b)                being selected independently from each other from H, a                substituted or unsubstituted C₁-C₁₂ alkyl, in particular                C₁-C₄ alkyl, a substituted or unsubstituted C₂-C₁₂                alkenyl, in particular C₂-C₄ alkenyl, or a substituted                or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄                alkynyl, with r being 1, 2, 3 or 4, in particular r is                1, or            -   o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular 0, 1,                2 or 3, more particularly 0 or 1, and each Z² is                selected independently from any other Z² from —F, —Cl,                —Br, —I, CN, —R^(b), —OR^(b), CH₂OR^(b) or —NR^(b) ₂, in                particular from —F, —Cl, —R^(b), —OR^(b), CH₂OR^(b) or                —NR^(b) ₂, more particularly from —F, —Cl, —R^(b), with                each R^(b) being selected independently from each other                from H, a substituted or unsubstituted C₁-C₁₂ alkyl, in                particular C₁-C₄ alkyl, a substituted or unsubstituted                C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a                substituted or unsubstituted C₂-C₁₂ alkynyl, in                particular C₂-C₄ alkynyl, or            -   o of Z² _(o) is 0, 1, 2, 3, 4 or 5, in particular 0, 1,                2 or 3, more particularly 0 or 1, and each Z² is                selected independently from any other Z² from —F, —Cl,                —Br, —I or —R^(b), in particular from R^(b), with R^(b)                being selected from a substituted or unsubstituted                C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted                or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄                alkenyl or a substituted or unsubstituted C₂-C₁₂                alkynyl, in particular C₂-C₄ alkynyl,            -   o of Z² _(o) is 0, or                R² is selected from

with A being —(CH)(CH₃)₃, —(CH₂)CN, —(CH₂)C(═O)ONH₂, —(CH₂)N(CH₂CH₃)₂,—(CH₂)CH₂OH, —(CH₂)C(═O)NH₂.

Particular embodiment is given below:

Concerning further embodiments of R² reference is made to the firstaspect of the invention, particularly to the first sub aspect of firstaspect of the invention.

Concerning further embodiments of o of Z² _(o) and Z² reference is madeto the first aspect of the invention, particularly to the first subaspect of first aspect of the invention.

In some embodiments of a third sub aspect of the first aspect,

each of R² and R³ are selected independently from each other from

-   -   a substituted or unsubstituted alkyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkyl,    -   a substituted or unsubstituted alkoxy, in particular a        substituted or unsubstituted C₁-C₁₂ alkoxy,    -   a substituted or unsubstituted alkenyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkenyl,    -   a substituted or unsubstituted alkynyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkynyl,    -   a substituted or unsubstituted cycloalkyl, in particular a        substituted or unsubstituted C₃-C₁₀ cycloalkyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl,    -   a substituted or unsubstituted saturated heterocycle, in        particular a substituted or unsubstituted C₃-C₁₀ heterocycle, or    -   a substituted or unsubstituted heteroaryl, in particular a        substituted or unsubstituted C₅-C₁₀ heteroaryl, and        R¹ comprises    -   a. the general formula 2b′ to 2d′ and 2f′ to 2j′,

-   -   -   with D being a C₁ to C₄ alkyl, or R¹ comprises the general            formula 2b to 2d and 2f to 2j

-   -   with each T being selected independently from each other from        —CH₂, —NH, —S, —O, —CHCH₃, —C(CH₃)₂ or —NR^(c), in particular        from NH, —S or —O, and    -   with T′ being selected from —CH₂, —NH, —S, —O, —CHCH₃, —C(CH₃)₂        or —NR^(c), and    -   with each T″ being selected independently from each other from        being selected from —CH or ═N,    -   with R⁴ and R⁵ being selected independently from each other from        —H, —F, —CH₃, —CH₂CH₃, —OCH₃, —CH₂CF₃, —CHFCF₃, —CF₂CF₃, —CHF₂,        —CH₂F or —CF₃, in particular with R⁵ and R⁶ being selected        independently from each other from H, —F or —CH₃, and    -   with R⁶ being selected from —OH, —OCH₃, —OCH₂CH₃, —CH₃ or H,    -   with R⁷ being selected from ═NH, ═S or ═O, in particular from O,        and    -   with n of Z¹ _(n) being 0, 1, 2 or 3, in particular n of Z¹ _(n)        being 0 or 1, and with each Z¹ independently from any other Z¹        being selected from —F, —Cl, —Br, —I, CN, —R^(a), —OR^(a),        —(CH₂)_(r)OR^(a), —SR^(a), —(CH₂)_(r)SR^(a) or —NR^(a) ₂, with        each R^(a) being selected independently from each other from H,        a substituted or unsubstituted C₁-C₈ alkyl, in particular C₁-C₄        alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, in        particular C₂-C₄ alkenyl, or a substituted or unsubstituted        C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl, with r being 1, 2, 3        or 4, in particular r is 1,        with R^(c) being —CH₂OH, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH(CH₃)₂,        —CH₂CF₃, —CHFCF₃, —CF₂CF₃, —CHF₂, —CH₂F, —CF₃.

In some embodiments, particularly of the third sub aspect, R¹ comprisesthe general formula 2b to 2h, in particular the formula 2b, 2c, 2g or2h, more particularly the formula 2b, 2c, 2g or 2h.

In some embodiments, particularly of the third sub aspect, R¹ comprisesthe general formula 2b or 2c, in particular 2c.

In some embodiments, particularly of the third sub aspect,

-   -   T′ of the compound according to formula 2b or 2c is selected        from —NH, —S, —O or —NR^(c), wherein in particular T′ is S or        —NH, and T″ being selected from —CH or ═N, and with R⁶ being        selected from —CH₃ or H, in particular R⁶ is H,    -   each T of the compound according to formula 2d being selected        independently from each other from —NH, —S, —O or —NR^(c), in        particular at least one T is selected from NH or —NCH₃, more        particularly the T in the position 4, with respect to the        connection to the parent moiety, is —NH, and with R⁷ being        selected from ═NH, ═S or ═O, in particular from O, and    -   each T″ of the compound according to formula 2f is selected        independently from each other from —CH or ═N, in particular each        T″ is ═N,    -   T′ of the compound according to formula 2g or 2h is selected        from —NH, —S, —O or —NR^(c), wherein in particular T′ is —NR or        —NH, and T″ being selected from —CH or ═N, in particular T″ is        ═N,    -   T′ of the compound according to formula 2i or 2j is selected        from —NH or —NR^(c), wherein in particular T′ is —NH, and T″ is        ═N.

In some embodiments, particularly of the third sub aspect, R^(c) isselected from —CH₂OH, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃ or —CH(CH₃)₂, inparticular from —CH₃, —CH₂CH₃ or —CH(CH₃)₂, more particularly R^(c) isCH₃.

Concerning further embodiments of n of Z¹ _(n) and Z¹ _(n) reference ismade to the first aspect of the invention, particularly to the first subaspect of first aspect of the invention.

Concerning further embodiments of R² reference is made to the firstaspect of the invention, particularly to the second sub aspect of firstaspect of the invention.

Concerning further embodiments of o of Z² _(o) and Z² _(o) reference ismade to the first aspect of the invention, particularly to the first subaspect of first aspect of the invention.

Concerning further embodiments of R³ reference is made to the firstaspect of the invention, particularly to the second sub aspect of firstaspect of the invention.

In some embodiments, particularly of the third sub aspect, R³ isselected from

-   -   a substituted or unsubstituted C₁-C₄ alkyl,    -   a substituted or unsubstituted C₁-C₄ alkenyl,    -   a substituted or unsubstituted C₁-C₄ alkynyl,    -   a substituted or unsubstituted C₆ aryl,    -   a substituted or unsubstituted C₆-cycloalkyl or        a substituted or unsubstituted C₅-C₆— heteroaryl, in particular        a substituted or unsubstituted C₆-cycloalkyl or a substituted or        unsubstituted C₅-C₆— heteroaryl.

Concerning further more specific embodiments of R³ reference is made tothe first aspect of the invention, particularly to the second sub aspectof first aspect of the invention.

Concerning further embodiments of p of Z³ _(p) and Z³ _(p) reference ismade to the first aspect of the invention, particularly to the first subaspect of first aspect of the invention.

Particular embodiments of this sub aspect are given below:

ETI-T-compound IUPAC name 04_A_N(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(p-tolylimino)-3-phenylthiazolidin-4-one 04_B_I(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(4-fluorophenylimino)-3-cyclohexylthiazolidin-4-one 04_A_X(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(p-tolylimino)-3-isobutylthiazolidin-4-one 04_F_N(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(4-methoxyphenylimino)-3-phenylthiazolidin-4-one 04(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 03_T_N(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(2-chlorobenzylimino)-3-phenylthiazolidin-4-one 32(2Z,5Z)-5-((benzo[d]thiazol-6-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 03_A_A(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(p-tolylimino)-3-p-tolylthiazolidin-4-one 32_A_X(2Z,5Z)-2-(p-tolylimino)-5-((benzo[d]thiazol-6-yl)methylene)-3-isobutylthiazolidin-4-one 32_A_I(2Z,5Z)-2-(p-tolylimino)-5-((benzo[d]thiazol-6-yl)methylene)-3-cyclohexylthiazolidin-4-one 28_A_X(2Z,5Z)-2-(p-tolylimino)-3-isobutyl-5-((1-methyl-1H-indazol-5-yl)methylene)thiazolidin-4-one 28_A_I(2Z,5Z)-2-(p-tolylimino)-3-cyclohexyl-5-((1-methyl-1H-indazol-5-yl)methylene)thiazolidin-4-one 04_A_A(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(p-tolylimino)-3-p-tolylthiazolidin-4-one 03_P_N(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(4-fluorobenzylimino)-3-phenylthiazolidin-4-one 03_B_X(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(4-fluorophenylimino)-3-isobutylthiazolidin-4-one 04_C_F(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3-(4-methoxyphenyl)thiazolidin-4-one 03_U_N(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(phenethylimino)-3-phenylthiazolidin-4-one 28(2Z,5Z)-5-((1-methyl-1H-indazol-5-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 04_B_A(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(4-fluorophenylimino)-3-p-tolylthiazolidin-4-one 04_N_G(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-3-butyl-2-(phenylimino)thiazolidin-4-one 03_C_K(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(benzylimino)-3-(3-phenylpropyl)thiazolidin-4-one 03_N_K(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(phenylimino)-3-(3-phenylpropyl)thiazolidin-4-one 04_B_X(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(4-fluorophenylimino)-3-isobutylthiazolidin-4-one 03_N_C(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-3-benzyl-2-(phenylimino)thiazolidin-4-one 32_B_A(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(4-fluorophenylimino)-3-p-tolylthiazolidin-4-one 03_N_G(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-3-butyl-2-(phenylimino)thiazolidin-4- 03_C_O(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(benzylimino)-3-phenethylthiazolidin-4-one 04_N_K(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(phenylimino)-3-(3-phenylpropyl)thiazolidin-4-one 03(2Z,5Z)-5-((1H-indol-5-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 03_B_A(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(4-fluorophenylimino)-3-p-tolylthiazolidin-4-one 04_C_B(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3-(4-fluorophenyl)thiazolidin-4-one 04_S_N(2Z,5Z)-2-((pyridin-3-yl)methylimino)-5-((1H-benzo[d]imidazol-5-yl)methylene)-3-phenylthiazolidin-4-one 03_N_M(2Z,5Z)-5-((1H-indol-5-yl)methylene)-3-((furan-2-yl)methyl)-2-(phenylimino)thiazolidin-4-one 32_B_X(2Z,5Z)-2-(4-fluorophenylimino)-5-((benzo[d]thiazol-6-yl)methylene)-3-isobutylthiazolidin-4-one 04_P_N(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(4-fluorobenzylimino)-3-phenylthiazolidin-4-one 04_C_G(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3-butylthiazolidin-4-one 03_F_N(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(4-methoxyphenylimino)-3-phenylthiazolidin-4-one 04_C_O(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3-phenethylthiazolidin-4-one 04_C_K(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3-(3-phenylpropyl)thiazolidin-4-one 04_U_N(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(phenethylimino)-3-phenylthiazolidin-4-one 04_D_N(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(5-methylpyridin-2-ylimino)-3-phenylthiazolidin-4-one 28_B_I(2Z,5Z)-2-(4-fluorophenylimino)-3-cyclohexyl-5-((1-methyl-1H-indazol-5-yl)methylene)thiazolidin-4-one 04_N_M(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-3-((furan-2-yl)methyl)-2-(phenylimino)thiazolidin-4-one 04_C_N(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3-phenylthiazolidin-4-one 04_C_C(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-3-benzyl-2-(benzylimino)thiazolidin-4-one 04_N_C(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-3-benzyl-2-(phenylimino)thiazolidin-4-one 09(2Z,5Z)-5-((1H-indol-6-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 03_C_B(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(benzylimino)-3-(4-fluorophenyl)thiazolidin-4-one 03_D_N(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(5-methylpyridin-2-ylimino)-3-phenylthiazolidin-4-one 04_C_N(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3-phenylthiazolidin-4-one 28_B_A(2Z,5Z)-2-(4-fluorophenylimino)-5-((1-methyl-1H-indazol-5-yl)methylene)-3-p-tolylthiazolidin-4-one 26(2Z,5Z)-5-((benzofuran-5-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 28_A_A(2Z,5Z)-2-(4-fluorophenylimino)-5-((1-methyl-1H-indazol-5-yl)methylene)-3-p-tolylthiazolidin-4-one 30(2Z,5Z)-5-((benzo[b]thiophen-5-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 03_C_G(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(benzylimino)-3-butylthiazolidin-4-one 206-((13Z)-((Z)-4-oxo-3-phenyl-2-(phenylimino)thiazolidin-5-ylidene)methyl)benzo[d]oxazol-2(3H)-one 11(2Z,5Z)-3-phenyl-2-(phenylimino)-5-((quinoxalin-6-yl)methylene)thiazolidin-4-one 04_R_N(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(4-tert-butylbenzylimino)-3-phenylthiazolidin-4-one 31(2Z,5Z)-5-((benzo[d]thiazol-5-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 03_E_N(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(methylimino)-3-phenylthiazolidin-4-one 03_A_V(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(p-tolylimino)-3-dodecylthiazolidin-4-one 16(2Z,5Z)-5-((2-methylbenzo[d]thiazol-6-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 173-methyl-6-((18Z)-((Z)-4-oxo-3-phenyl-2-(phenylimino)thiazolidin-5-ylidene)methyl)benzo[d]thiazol-2(3H)-one 215-((18Z)-((Z)-4-oxo-3-phenyl-2-(phenylimino)thiazolidin-5-ylidene)methyl)-1H-benzo[d]imidazol-2(3H)-one 03_N_F(2Z,5Z)-5-((1H-indol-5-yl)methylene)-3-(4-methoxyphenyl)-2-(phenylimino)thiazolidin-4-one 03_Q_N(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(4-methoxybenzylimino)-3-phenylthiazolidin-4-one 03_R_N(2Z,5Z)-5-((1H-indol-5-yl)methylene)-2-(4-tert-butylbenzylimino)-3-phenylthiazolidin-4- 04_E_N(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(methylimino)-3-phenylthiazolidin-4-one 04_N_F(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-3-(4-methoxyphenyl)-2-(phenylimino)thiazolidin-4-one 04_T_N(2Z,5Z)-5-((1H-benzo[d]imidazol-5-yl)methylene)-2-(2-chlorobenzylimino)-3-phenylthiazolidin-4-one

According to the second aspect the invention relates to a compoundcharacterized by a general formula 1

-   -   wherein    -   R² is selected from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl, and    -   each of R¹ and R³ are selected independently from each other        from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl.

In some embodiments, R² is selected from a moiety described in theembodiments of the first aspect of the invention concerning thesubstituent R². Reference made to the detailed description above, inorder to avoid repetition.

In some embodiments, R¹ is selected from a moiety described in theembodiments of the first aspect of the invention concerning thesubstituent R¹. Reference made to the detailed description above, inorder to avoid repetition.

In some embodiments, R³ is selected from a moiety described in theembodiments of the first aspect of the invention concerning thesubstituent R³. Reference made to the detailed description above, inorder to avoid repetition.

Any embodiment described for R¹ or R³ according to the second aspect ofthe invention may be combined with any embodiment described for R²according to the second aspect of the invention.

According to the third aspect the invention relates to a compoundcharacterized by a general formula 1

-   -   wherein    -   R³ is selected from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl, and    -   each of R¹ and R² are selected independently from each other        from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl.

In some embodiments, R³ is selected from a moiety described in theembodiments of the first aspect of the invention concerning thesubstituent R³. Reference made to the detailed description above, inorder to avoid repetition.

In some embodiments, R¹ is selected from a moiety described in theembodiments of the first aspect of the invention concerning thesubstituent R¹. Reference made to the detailed description above, inorder to avoid repetition.

In some embodiments, R² is selected from a moiety described in theembodiments of the first aspect of the invention concerning thesubstituent R². Reference made to the detailed description above, inorder to avoid repetition.

Any embodiment described for R¹ or R² according to the third aspect ofthe invention may be combined with any embodiment described for R³according to the third aspect of the invention.

According to the fourth aspect the invention relates to a compoundcomprising the following general formula (1)

-   -   wherein    -   R¹ is selected from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl, and    -   each of R² and R³ are selected independently from each other        from        -   a substituted or unsubstituted alkyl, in particular a            substituted or unsubstituted C₁-C₁₂ alkyl,        -   a substituted or unsubstituted alkoxy, in particular a            substituted or unsubstituted C₁-C₁₂ alkoxy,        -   a substituted or unsubstituted alkenyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkenyl,        -   a substituted or unsubstituted alkynyl, in particular a            substituted or unsubstituted C₂-C₁₂ alkynyl,        -   a substituted or unsubstituted cycloalkyl, in particular a            substituted or unsubstituted C₃-C₁₀ cycloalkyl,        -   a substituted or unsubstituted aryl, in particular a            substituted or unsubstituted C₆-C₁₀ aryl,        -   a substituted or unsubstituted heterocycle, in particular a            substituted or unsubstituted C₃-C₁₀ heterocycle, or        -   a substituted or unsubstituted heteroaryl, in particular a            substituted or unsubstituted C₅-C₁₀ heteroaryl.

In some embodiments, R¹ is selected from

-   -   a substituted or unsubstituted alkyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkyl,    -   a substituted or unsubstituted alkoxy, in particular a        substituted or unsubstituted C₁-C₁₂ alkoxy,    -   a substituted or unsubstituted alkenyl, in particular a        substituted or unsubstituted C₁₂-C₁₂ alkenyl,    -   a substituted or unsubstituted alkynyl, in particular a        substituted or unsubstituted C₂-C₁₂ alkynyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl.

In some embodiments, R¹ is selected from

-   -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula -M-Ar,        -   with M being            -   an alkyl, in particular a C₁-C₁₂ alkyl, more                particularly a C₁-C₄ alkyl,            -   an alkenyl, in particular a C₂-C₁₂ alkenyl, more                particularly a C₂-C₄ alkenyl,            -   an alkynyl, in particular a C₂-C₁₂ alkynyl, more                particularly a C₂-C₄ alkynyl, and            -   Ar being a substituted or unsubstituted C₅-C₆— aryl or a                substituted or unsubstituted C₅-C₆— heteroaryl, or    -   a substituted or unsubstituted C₆— aryl, wherein in particular        the substituted C₆— aryl comprises at least one substituent Z¹⁰.

In some embodiments, R¹ is selected from

-   -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula 6a

or

-   -   a substituted or unsubstituted C₆— aryl, wherein the substituted        C₆ aryl comprises the formula 6b

-   -   with M being        -   an alkyl, in particular a C₁-C₁₂ alkyl, more particularly a            C₁-C₄ alkyl,        -   an alkenyl, in particular a C₂-C₁₂ alkenyl, more            particularly a C₂-C₄ alkenyl,        -   an alkynyl, in particular a C₂-C₁₂ alkynyl, more            particularly a C₂-C₄ alkynyl, and    -   l of Z¹⁰ _(l) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3,        more particularly 0 or 1, and    -   each Z¹⁰ independently from any other Z¹⁰ is selected from —F,        —Cl, —Br, —I, CN, —R^(e), —OR^(e), —(CH₂)_(r)OR^(e), —SR^(e),        —(CH₂)_(r)SR^(e) or —NR^(e) ₂, with each R^(e) being selected        independently from each other from H, a substituted or        unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a        substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄        alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, in        particular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in        particular r is 1.

In some embodiments, R¹ is selected from

-   -   a substituted alkyl, wherein the substituted alkyl comprises the        formula 6a

or

-   -   a substituted or unsubstituted C₆— aryl, wherein the C₆ aryl        comprises the formula 6b

-   -   with M being        -   an alkyl, in particular a C₁-C₁₂ alkyl, more particularly a            C₁-C₄ alkyl, and    -   l of Z¹⁰ _(l) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3,        more particularly 0 or 1, and    -   each Z¹⁰ independently from any other Z¹⁰ is selected from —F,        —Cl, —Br, —I, CN, —R^(e), —OR^(e), —(CH₂)_(r)OR^(e), —SR^(e),        —(CH₂)_(r)SR^(e) or —NR^(e) ₂, with each R^(e) being selected        independently from each other from H, a substituted or        unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a        substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄        alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, in        particular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in        particular r is 1.

In some embodiments, R¹ is selected from

-   -   a substituted or unsubstituted C₆— aryl, wherein the C₆ aryl        comprises the formula 6b

-   -   with l of Z¹⁰ _(l) being 0, 1, 2, 3, 4 or 5, in particular 0, 1,        2 or 3, more particularly 0 or 1, and    -   each Z¹⁰ independently from any other Z¹⁰ is selected from —F,        —Cl, —Br, —I, CN, —R^(e), —OR^(e), —(CH₂)_(r)OR^(e), —SR^(e),        —(CH₂)_(r)SR^(e) or —NR^(e) ₂, with each R^(e) being selected        independently from each other from H, a substituted or        unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a        substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄        alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, in        particular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in        particular r is 1.

In some embodiments, R¹ is selected from

-   -   a substituted or unsubstituted C₆— aryl, wherein the substituted        C₆ aryl comprises the formula 6b

-   -   l of Z¹⁰ _(l) is 1, 2, 3, 4 or 5, in particular 1, 2 or 3, more        particularly 1, and    -   each Z¹⁰ independently from any other Z¹⁰ is selected from —F,        —Cl, —Br, —I, CN, —R^(e), —OR^(e), —(CH₂)_(r)OR^(e), —SR^(e),        —(CH₂)_(r)SR^(e) or —NR^(e) ₂, with each R^(e) being selected        independently from each other from H, a substituted or        unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a        substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄        alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, in        particular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in        particular r is 1, wherein at least one Z¹⁰ is —(CH₂)_(r)OR^(e),        in particular in position 3.

In some embodiments, l of Z¹⁰ _(l) is 0, 1, 2, 3, 4 or 5, in particular0, 1, 2 or 3, more particularly 0 or 1, and each Z¹⁰ is selectedindependently from any other Z¹⁰ from —F, —Cl, —Br, —I, CN, —R^(e),—SR^(e), —CH₂SR^(e), —OR^(e), CH₂OR^(e) or —NR^(e) ₂, in particular from—F, —Cl, CN, —R^(e), —OR^(e), —CH₂OR^(e) or —NR^(e) ₂, more particularlyfrom CN, —OR^(e) or CH₂OR^(e), with each R^(e) being selectedindependently from each other from H, a substituted or unsubstitutedC₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted or unsubstitutedC₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted orunsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, l of Z¹⁰ _(l) is 0, 1, 2, 3, 4 or 5, in particular0, 1, 2 or 3, more particularly 0 or 1, and each Z³ is selectedindependently from any other Z³ from —F, —Cl, —Br, —I, CN, —OR^(e) or—CH₂OR^(e), in particular from R^(e), with R^(e) being selected from asubstituted or unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, asubstituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenylor a substituted or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄alkynyl.

In some embodiments, l of Z¹⁰ _(l) is 1, 2, 3, 4 or 5, in particular 1,2 or 3, more particularly 1, and each Z¹⁰ is selected independently fromany other Z¹⁰ from —F, —Cl, —Br, —I, CN, —R^(e), —SR^(e), —CH₂SR^(e),—OR^(e), CH₂OR^(e) or —NR^(e) ₂, in particular from —F, —Cl, CN, —R^(e),—OR^(e), —CH₂OR^(e) or —NR^(e) ₂, more particularly from CN, —OR^(e) orCH₂OR^(e), with each R^(e) being selected independently from each otherfrom H, a substituted or unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, in particularC₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, inparticular C₂-C₄ alkynyl.

In some embodiments, l of Z¹⁰ _(l) is 1, 2, 3, 4 or 5, in particular 1,2 or 3, more particularly 1, and each Z³ is selected independently fromany other Z³ from —F, —Cl, —Br, —I, CN, —OR^(e) or —CH₂OR^(e), inparticular from R^(e), with R^(e) being selected from a substituted orunsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a substituted orunsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl or asubstituted or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄alkynyl.

In some embodiments, l of Z¹⁰ _(l) is 1 or 2, in particular 1.

In some embodiments, l of Z¹⁰ _(l) the at least one Z¹⁰ is—(CH₂)_(r)OR^(e), in particular in position 3, with R^(e) being H orCH₃, with r being selected from 1, 2, 3, in particular with r being 1.

In some embodiments, l of Z¹⁰ _(l) is 0, 1 or 2, in particular 0 or 1.

In some embodiments, R¹ is selected from.

or derivatives thereof.

In some embodiments, R¹ is selected from.

or derivatives thereof.

In some embodiments, R¹ is selected from

In some embodiments, R² is selected from a moiety described in theembodiments of the first aspect of the invention concerning thesubstituent R². Reference made to the detailed description above, inorder to avoid repetition.

In some embodiments, R³ is selected from a moiety described in theembodiments of the first aspect of the invention concerning thesubstituent R³. Reference made to the detailed description above, inorder to avoid repetition.

Any embodiment described for R² or R³ according to the fourth aspect ofthe invention may be combined with any embodiment described for R¹according to the fourth aspect of the invention.

Particular embodiments are given below:

ETI-T-compound IUPAC name 22_K_N(2Z,5Z)-2-(3-phenylpropylimino)-5-(4-(hydroxymethyl)benzylidene)-3-phenylthiazolidin-4-one 22_A_N(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(p-tolylimino)-3-phenylthiazolidin-4-one 22_B_X(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-fluorophenylimino)-3-isobutylthiazolidin-4-one 22_F_N(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-methoxyphenylimino)-3-phenylthiazolidin-4-one 22_A_X(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(p-tolylimino)-3-isobutylthiazolidin-4- 22_A_A(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(p-tolylimino)-3-p-tolylthiazolidin-4-one 15_Q_N(2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-2-(4-methoxybenzylimino)-3-phenylthiazolidin-4-one 22_B_A(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-fluorophenylimino)-3-p-tolylthiazolidin-4-one 22_P_N(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-fluorobenzylimino)-3-phenylthiazolidin-4-one 22_C_F(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3-(4-methoxyphenyl)thiazolidin-4-one 22_N_C(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-benzyl-2-(phenylimino)thiazolidin-4-one 15_C_K(2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-2-(benzylimino)-3-(3-phenylpropyl)thiazolidin-4-one 22_Q_N(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-methoxybenzylimino)-3-phenylthiazolidin-4-one 22(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 22_U_N(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(phenethylimino)-3-phenylthiazolidin-4-one 22_N_K(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(phenylimino)-3-(3-phenylpropyl)thiazolidin-4- 15(2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 22_N_G(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-butyl-2-(phenylimino)thiazolidin-4-one 22_C_O(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3-phenethylthiazolidin-4- 22_C_G(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3-butylthiazolidin-4-one 22_N_M(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-((furan-2-yl)methyl)-2-(phenylimino)thiazolidin-4-one 22_C_K(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3-(3-phenylpropyl)thiazolidin-4- 22_D_N(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(5-methylpyridin-2-ylimino)-3-phenylthiazolidin-4-one 15_C_O(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3-phenethylthiazolidin-4-one 22_C_N(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3-phenylthiazolidin-4-one 15_C_N(2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-2-(benzylimino)-3-phenylthiazolidin-4- 22_C_B(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3-(4-fluorophenyl)thiazolidin-4-one 15_T_N(2Z,5Z)-2-(2-chlorobenzylimino)-5-(3-(methoxymethyl)benzylidene)-3-phenylthiazolidin-4-one 22_R_N(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-tert-butylbenzylimino)-3-phenylthiazolidin-4-one 22_C_C(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-benzyl-2-(benzylimino)thiazolidin-4-one 23_A_V(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-fluorophenylimino)-3-dodecylthiazolidin-4-one 22_B_V(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-fluorophenylimino)-3-dodecylthiazolidin-4-one 15_U_N(2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-2-(phenethylimino)-3-phenylthiazolidin-4-one 34(2Z,5Z)-5-(4-(methoxymethyl)benzylidene)-3-phenyl-2-(phenylimino)thiazolidin-4-one 04_A_V(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(p-tolylimino)-3-dodecylthiazolidin-4-one 15_R_N(2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-2-(4-tert-butylbenzylimino)-3-phenylthiazolidin-4-one 22_A_V(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(p-tolylimino)-3-dodecylthiazolidin-4-one 22_E_N(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(methylimino)-3-phenylthiazolidin-4-one 22_N_F(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-(4-methoxyphenyl)-2-(phenylimino)thiazolidin-4-one 22_T_N(2Z,5Z)-2-(2-chlorobenzylimino)-5-(4-(hydroxymethyl)benzylidene)-3-phenylthiazolidin-4-one

In some embodiments of a first sub aspect of the fourth aspect of theinvention

R¹ is selected from

-   -   a substituted or unsubstituted alkyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkyl,    -   a substituted or unsubstituted alkoxy, in particular a        substituted or unsubstituted C₁-C₁₂ alkoxy,    -   a substituted or unsubstituted alkenyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkenyl,    -   a substituted or unsubstituted alkynyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkynyl,    -   a substituted or unsubstituted cycloalkyl, in particular a        substituted or unsubstituted C₃-C₁₀ cycloalkyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl, and        each of R² and R³ are selected independently from each other        from    -   a substituted or unsubstituted alkyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkyl,    -   a substituted or unsubstituted alkoxy, in particular a        substituted or unsubstituted C₁-C₁₂ alkoxy,    -   a substituted or unsubstituted alkenyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkenyl,    -   a substituted or unsubstituted alkynyl, in particular a        substituted or unsubstituted C₁-C₁₂ alkynyl,    -   a substituted or unsubstituted cycloalkyl, in particular a        substituted or unsubstituted C₃-C₁₀ cycloalkyl,    -   a substituted or unsubstituted aryl, in particular a substituted        or unsubstituted C₆-C₁₀ aryl,    -   a substituted or unsubstituted saturated heterocycle, in        particular a substituted or unsubstituted C₃-C₁₀ heterocycle, or    -   a substituted or unsubstituted heteroaryl, in particular a        substituted or unsubstituted C₅-C₀₁ heteroaryl,        wherein at least one of R₁, R₂ and R₃ is selected form,    -   in case of R₁,    -   from        -   a substituted alkyl, alkenyl or alkynyl, wherein the            substituted alkyl, alkenyl or alkynyl comprises the formula            -M-Ar,            -   with M being                -   an alkyl, in particular a C₁-C₁₂ alkyl, more                    particularly a C₁-C₄ alkyl,                -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more                    particularly a C₁-C₄ alkenyl,                -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more                    particularly a C₁-C₄ alkynyl, and            -   Ar being a C₆— aryl, wherein in particular the                substituted C₆— aryl comprises at least one substituent                Z¹⁰,    -   in case of R₂ from        -   a substituted alkyl, alkenyl or alkynyl, wherein the            substituted alkyl, alkenyl or alkynyl comprises the formula            -L-Ar,            -   with L being                -   an alkyl, in particular a C₁-C₁₂ alkyl, more                    particularly a C₁-C₄ alkyl,                -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more                    particularly a C₁-C₄ alkenyl,                -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more                    particularly a C₁-C₄ alkynyl, and                -   Ar being a substituted or unsubstituted C₅-C₆— aryl                    or a substituted or unsubstituted C₅-C₆— heteroaryl,                    or        -   a substituted or unsubstituted C₆— aryl or a substituted or            unsubstituted C₅-C₆-heteroaryl, wherein in particular the            substituted C₆— aryl or the substituted C₅-C₆-heteroaryl            comprises at least one substituent Z², and    -   in case of R₃ from        -   a substituted alkyl, alkenyl or alkynyl, wherein the            substituted alkyl, alkenyl or alkynyl comprises the formula            -D-Ar,            -   with D being                -   an alkyl, in particular a C₁-C₁₂ alkyl, more                    particularly a C₁-C₄ alkyl,                -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more                    particularly a C₁-C₄ alkenyl,                -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more                    particularly a C₁-C₄ alkynyl, and                -   Ar being a substituted or unsubstituted C₅-C₆— aryl                    or a substituted or unsubstituted C₅-C₆— heteroaryl,                    or                -   a substituted or unsubstituted C₆— aryl or a                    substituted or unsubstituted C₅-C₆— heteroaryl,                    wherein in particular the substituted C₆— aryl or                    the substituted C₅-C₆— heteroaryl comprises at least                    one substituent Z³

In some embodiments, particularly of the first aspect of the fourthinvention, R¹ is selected from

-   -   a substituted alkyl, alkenyl or alkynyl, wherein the substituted        alkyl, alkenyl or alkynyl comprises the formula 6a

or

-   -   with M being        -   an alkyl, in particular a C₁-C₁₂ alkyl, more particularly a            C₁-C₄ alkyl,        -   an alkenyl, in particular a C₁-C₁₂ alkenyl, more            particularly a C₁-C₄ alkenyl,        -   an alkynyl, in particular a C₁-C₁₂ alkynyl, more            particularly a C₁-C₄ alkynyl, and    -   l of Z¹⁰ _(l) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3,        more particularly 0 or 1, and        each Z¹⁰ independently from any other Z¹⁰ is selected from —F,        —Cl, —Br, —I, CN, —R^(e), —OR^(e), —(CH₂)_(r)OR^(e), —SR^(e),        —(CH₂)_(r)SR^(e) or —NR^(e) ₂, with each R^(e) being selected        independently from each other from H, a substituted or        unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a        substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄        alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, in        particular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in        particular r is 1.

In some embodiments, particularly of the first aspect of the fourthinvention, R¹ is selected from wherein R¹ is selected from

-   -   a substituted alkyl, wherein the substituted alkyl comprises the        formula 6a

-   -   with M being        -   an alkyl, in particular a C₁-C₁₂ alkyl, more particularly a            C₁-C₄ alkyl, and    -   l of Z¹⁰ _(l) is 0, 1, 2, 3, 4 or 5, in particular 0, 1, 2 or 3,        more particularly 0 or 1, and    -   each Z¹⁰ independently from any other Z¹⁰ is selected from —F,        —Cl, —Br, —I, CN, —R^(e), —OR^(e), —(CH₂)_(r)OR^(e), —SR^(e),        —(CH₂)_(r)SR^(e) or —NR^(e) ₂, with each R^(e) being selected        independently from each other from H, a substituted or        unsubstituted C₁-C₁₂ alkyl, in particular C₁-C₄ alkyl, a        substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄        alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, in        particular C₂-C₄ alkynyl, with r being 1, 2, 3 or 4, in        particular r is 1

Concerning further embodiments of l of Z¹⁰ _(l) and Z¹⁰ _(l) referenceis made to the first aspect of the invention, particularly to the firstsub aspect of first aspect of the invention.

Concerning further embodiments of R² reference is made to the firstaspect of the invention, particularly to the second sub aspect of firstaspect of the invention.

Concerning further embodiments of o of Z² _(o) and Z² _(o) reference ismade to the first aspect of the invention, particularly to the first subaspect of first aspect of the invention.

Concerning further embodiments of R³ reference is made to the firstaspect of the invention, particularly to the second sub aspect of firstaspect of the invention.

In some embodiments, particularly of the third sub aspect, R³ isselected from

-   -   a substituted or unsubstituted C₁-C₄ alkyl,    -   a substituted or unsubstituted C₁-C₄ alkenyl,    -   a substituted or unsubstituted C₁-C₄ alkynyl,    -   a substituted or unsubstituted C₆ aryl,    -   a substituted or unsubstituted C₆-cycloalkyl or    -   a substituted or unsubstituted C₅-C₆— heteroaryl, in particular        a substituted or unsubstituted C₆-cycloalkyl or a substituted or        unsubstituted C₅-C₆— heteroaryl.

Concerning further more specific embodiments of R³ reference is made tothe first aspect of the invention, particularly to the second sub aspectof first aspect of the invention.

Concerning further embodiments of p of Z³ _(p) and Z³ _(p) reference ismade to the first aspect of the invention, particularly to the first subaspect of first aspect of the invention.

Particular embodiments are given below:

ETI-T-compound IUPAC name 23_C_N(2Z,5Z)-5-benzylidene-2-(benzylimino)-3-phenylthiazolidin-4-one 23_T_N(2Z,5Z)-2-(2-chlorobenzylimino)-5-benzylidene-3-phenylthiazolidin-4-one23_Q_N(2Z,5Z)-2-(4-methoxybenzylimino)-5-benzylidene-3-phenylthiazolidin-4-one 23_C_G(2Z,5Z)-5-benzylidene-2-(benzylimino)-3-butylthiazolidin-4-one 23_N_K(2Z,5Z)-5-benzylidene-2-(phenylimino)-3-(3-phenylpropyl)thiazolidin-4-one 23_B_X(2Z,5Z)-2-(4-fluorophenylimino)-5-benzylidene-3-isobutylthiazolidin-4-one 23_C_O(2Z,5Z)-5-benzylidene-2-(benzylimino)-3-phenethylthiazolidin-4-one23_N_M(2Z,5Z)-5-benzylidene-3-((furan-2-yl)methyl)-2-(phenylimino)thiazolidin-4-one 23_F_N(2Z,5Z)-2-(4-methoxyphenylimino)-5-benzylidene-3-phenylthiazolidin-4-one 23_A_A(2Z,5Z)-2-(p-tolylimino)-5-benzylidene-3-p-tolylthiazolidin-4-one 23(2Z,5Z)-5-benzylidene-3-phenyl-2-(phenylimino)thiazolidin-4-one 23_K_N(2Z,5Z)-2-(3-phenylpropylimino)-5-benzylidene-3-phenylthiazolidin-4- one23_A_N (2Z,5Z)-2-(p-tolylimino)-5-benzylidene-3-phenylthiazolidin-4-one23_N_G (2Z,5Z)-5-benzylidene-3-butyl-2-(phenylimino)thiazolidin-4-one23_N_C (2Z,5Z)-3-benzyl-5-benzylidene-2-(phenylimino)thiazolidin-4-one23_P_N(2Z,5Z)-2-(4-fluorobenzylimino)-5-benzylidene-3-phenylthiazolidin-4-one23_C_B(2Z,5Z)-5-benzylidene-2-(benzylimino)-3-(4-fluorophenyl)thiazolidin-4-one 23_E_N(2Z,5Z)-5-benzylidene-2-(methylimino)-3-phenylthiazolidin-4-one 23_C_K(2Z,5Z)-5-benzylidene-2-(benzylimino)-3-(3-phenylpropyl)thiazolidin-4-one 23_B_V(2Z,5Z)-2-(4-fluorophenylimino)-5-benzylidene-3-dodecylthiazolidin-4-one 23_D_N(2Z,5Z)-2-(5-methylpyridin-2-ylimino)-5-benzylidene-3-phenylthiazolidin-4-one 23_N_L(2Z,5Z)-5-benzylidene-3-(4-chlorophenyl)-2-(phenylimino)thiazolidin-4-one

In some embodiments the compound of the invention according to thefirst, second, third or fourth aspect of the invention comprises a(2Z,5Z), (2Z,5E), (2E,5Z) or (2E,5E) isomer form, in particular a(2Z,5Z) or (2Z,5E), more particularly a (2Z,5Z) isomer form,characterized by formula 1a

with the isomer center being indicated by the asterix (*),with R¹, R²and R³ having the same meaning as defined previously, wherein thecompound of the invention comprises the before mentioned isomers in anessentially pure form, with R¹, R² and R³ having the same meaning asdefined previously.

As used herein the term “essentially pure” refers to a purity of ≥90%,in particular of ≥95%.

In some embodiments the compound of the invention comprises a mixture ofthe (2Z,5Z), (2Z,5E), (2E,5Z) or (2E,5E) isomer forms, in particular amixture of (2Z,5Z) and (2Z,5E). characterized by formula 1a as depictedabove.

The following formulas show the respective configuration:

with R¹, R² and R³ having the same meaning as defined previously.

Particular embodiments of the invention are:

A fifth aspect of the invention relates to a compound according to thefirst, second, third or fourth aspect of the invention for use as amedicament.

A sixth aspect of the invention relates to a compound according to thefirst, second, third or fourth aspect of the invention for use in thetreatment of psychiatric or neurological disorders and inflammation, inparticular neuroinflammation.

A seventh aspect of the invention relates to a pharmaceuticalpreparation for use in the treatment of psychiatric or neurologicaldisorders and inflammation, in particular neuroinflammation, comprisingat least one compound according to the first, second, third or fourthaspect of the invention.

The compounds of the invention are potent inhibitors of AEA cellmembrane transport and do not inhibit the AEA metabolic enzyme FAAH. Thecompounds of the invention show both cannabimimetic behavioral effectsand antiinflammatory effects, in particular an anti-neuroinflammatoryeffect, as exemplified in the experimental section.

By inhibiting AEA uptake the ECS can be modulated in a unique way,leading to diverse pharmacological actions like analgesia,anti-inflammatory and CNS effects exemplified by the tetrad effect(Nicolussi & Gertsch, 2015, Vitam Horm. 98:441-85.).

The use of the compounds of the invention in a method for treatment ofpsychiatric or neurological disorders is related to attenuation ofneuroinflammation and neuronal retrograde signaling mediated viaendocannabinoids including AEA. Such diseases include bipolar diseases,schizophrenia, sleeping disorders, multiple sclerosis and Alzheimersdisease (Ashton and Moore Acta Psychiatr Scand. 2011, 124, 250-61; Asoand Ferrer I, Front Pharmacol. 2014, 5:37; Correa et al. Vitam Horm.2009, 81, 207-30.)

In some embodiments, the compounds of the general formula (1) may beisolated in form of salts, in particular in form of pharmaceuticallyacceptable salts. The same applies to all of the before mentionedembodiments. In some embodiments, the compounds of the general formula(1) may be isolated in form of a tautomer, a hydrate or a solvate.

Such salts are formed, for example, as acid addition salts, preferablywith organic or inorganic acids, from compounds of the general formula(1) with a basic nitrogen atom, in particular the pharmaceuticallyacceptable salts are formed in such a way. Suitable inorganic acids are,without being limited to, halogen acids, such as hydrochloric acid,sulfuric acid, or phosphoric acid and the like. Suitable organic acidsare, without being limited to, carboxylic, phosphonic, sulfonic orsulfamic acids and the like. Such organic acids may be, without beinglimited to, acetic acid, glycolic acid, lactic acid, malic acid,tartaric acid, or citric acid. Salts may also be formed, for example, assalts with organic or inorganic bases, from compounds of the generalformula (1) with a nitrogen atom bearing an acidic hydrogen. Examples ofsuitable cations are—without being limited to—sodium, potassium, calciumor magnesium cations, or cations of organic nitrogen bases, e.g.protonated mono-, di- or tri-(2-hydroxethyl)amine.

In view of the close relationship between the novel compounds in theirfree form and those in the form of their salts, any reference to thefree compounds hereinbefore and hereinafter is to be understood asreferring also to the corresponding salts, as appropriate and expedient.Likewise, in view of the close relationship between the novel compoundsof the general formula (1) and their tautomers, any reference to thecompounds of the general formula (1) is to be understood as referringalso to the corresponding tautomers. The same applies to a hydrate or asolvate.

In some embodiments, the pharmaceutical preparation comprises at leastone compound according to the invention as an active ingredient and atleast one pharmaceutically acceptable carrier. In some embodiments, thepharmaceutical preparation comprises at least one compound according tothe invention in its free form as an active ingredient. In someembodiments, the pharmaceutical preparation comprises at least onecompound according to the invention in its free form as an activeingredient and at least one pharmaceutically acceptable carrier.

In some embodiments, the pharmaceutical preparation comprises at leastone compound according to the invention in form of a salt, a tautomer, apharmaceutically acceptable salt, a hydrate or a solvate. In someembodiments, the pharmaceutical preparation comprises at least onecompound according to the invention in form of a salt, a tautomer, apharmaceutically acceptable salt, a hydrate or a solvate and at leastone pharmaceutically acceptable carrier.

Furthermore the invention relates to pharmaceutical preparationscomprising at least one compound mentioned herein before as activeingredient, which can be used especially in the treatment of thediseases mentioned. The pharmaceutical preparations may be used inparticular for a method for treatment of psychiatric disorders.

In some embodiments, the pharmaceutical preparations is for enteraladministration, such as nasal, buccal, rectal, local or, especially,oral administration, and for parenteral administration, such asintravenous, intramuscular or subcutaneous administration, areespecially preferred. The preparations comprise the active ingredientalone or, in particular, together with a pharmaceutically acceptablecarrier. The dosage of the active ingredient depends upon the disease tobe treated and upon the species, its age, weight, and individualcondition, the individual pharmacokinetic data, and the mode ofadministration. In particular, the oral application of the activeingredient is preferred.

In some embodiments, the pharmaceutical preparations comprise fromapproximately 1% to approximately 95% active ingredient. Unit dose formsare, for example, coated and uncoated tablets, ampoules, vials,suppositories, or capsules. Further dosage forms are, for example,ointments, creams, pastes, foams, tinctures, lip-sticks, drops, sprays,dispersions, etc. Examples are capsules containing from about 0.005 g toabout 1.0 g active ingredient.

In some embodiments, the pharmaceutical preparations of the presentinvention are prepared in a manner known per se, for example by means ofconventional mixing, granulating, coating, dissolving or lyophilizingprocesses.

In some embodiments, the pharmaceutical preparations is in form ofsolutions of the active ingredient, and also suspensions or dispersions,especially isotonic aqueous solutions, dispersions or suspensions which,for example in the case of lyophilized preparations comprising theactive ingredient alone or together with a carrier, for examplemannitol, can be made up before use.

In some embodiments, the pharmaceutical preparations may be sterilizedand/or may comprise excipients, for example preservatives, stabilizers,wetting agents and/or emulsifiers, solubilizers, salts for regulatingosmotic pressure and/or buffers and are prepared in a manner known perse, for example by means of conventional dissolving and lyophilizingprocesses. The said solutions or suspensions may compriseviscosity-increasing agents, typically sodium carboxymethylcellulose,carboxymethylcellulose, dextran, polyvinylpyrrolidone, or gelatins, oralso solubilizers, e.g. Tween 80® (polyoxyethylene(20)sorbitanmono-oleate).

In some embodiments, the pharmaceutical preparation comprisessuspensions in oil, which comprise as the oil component a vegetable,synthetic, or semi-synthetic oils customary for injection purposes. Insome embodiments, the pharmaceutical preparation comprises a mixtures offatty acid esters, vegetable oils such as, without being limited to,cottonseed oil, almond oil, olive oil, castor oil, sesame oil, soybeanoil and groundnut oil. The manufacture of injectable preparations isusually carried out under sterile conditions, as is the filling, forexample, into ampoules or vials, and the sealing of the containers.

Suitable carriers are especially fillers, such as sugars, for examplelactose, saccharose, mannitol or sorbitol, cellulose preparations,and/or calcium phosphates, for example tricalcium phosphate or calciumhydrogen phosphate, and also binders, such as starches, for examplecorn, wheat, rice or potato starch, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, and/orpolyvinylpyrrolidone, and/or, if desired, disintegrators, such as theabove-mentioned starches, also carboxymethyl starch, crosslinkedpolyvinyl pyrrolidone, alginic acid or a salt thereof, such as sodiumalginate. Additional excipients are especially flow conditioners andlubricants, for example silicic acid, talc, stearic acid or saltsthereof, such as magnesium or calcium stearate, and/or polyethyleneglycol, or derivatives thereof.

Tablet cores can be provided with suitable, optionally enteric, coatingsthrough the use of, inter alia, concentrated sugar solutions which maycomprise gum arabic, talc, polyvinylpyrrolidone, polyethylene glycoland/or titanium dioxide, or coating solutions in suitable organicsolvents or solvent mixtures, or, for the preparation of entericcoatings, solutions of suitable cellulose preparations, such asacetylcellulose phthalate or hydroxypropylmethylcellulose phthalate.Dyes or pigments may be added to the tablets or tablet coatings, forexample for identification purposes or to indicate different doses ofactive ingredient.

In some embodiments, the pharmaceutical preparation is suitable for oraladministration also include hard capsules consisting of gelatin, andalso soft, sealed capsules consisting of gelatin and a plasticizer, suchas glycerol or sorbitol. The hard capsules may contain the activeingredient in the form of granules, for example in admixture withfillers, such as corn starch, binders, and/or glidants, such as talc ormagnesium stearate, and optionally stabilizers. In soft capsules, theactive ingredient is preferably dissolved or suspended in suitableliquid excipients, such as fatty oils, paraffin oil or liquidpolyethylene glycols or fatty acid esters of ethylene or propyleneglycol, to which stabilizers and detergents, for example of the polyoxyethylene sorbitan fatty acid ester type, may also be added.

In some embodiments, the pharmaceutical preparation is suitable forrectal administration are, for example, suppositories that consist of acombination of the active ingredient and a suppository base. Suitablesuppository bases are, for example, natural or synthetic triglycerides,paraffin hydrocarbons, polyethylene glycols or higher alkanols.

In some embodiments, the pharmaceutical preparation is suitable forparenteral administration, aqueous solutions of an active ingredient inwater-soluble form or aqueous injection suspensions that containviscosity-increasing substances, for example sodiumcarboxymethylcellulose, sorbitol and/or dextran, and, if desired,stabilizers, are especially suitable. The active ingredient, optionallytogether with excipients, can also be in the form of a lyophilizate andcan be made into a solution before parenteral administration by theaddition of suitable solvents. Solutions such as are used, for example,for parenteral administration can also be employed as infusionsolutions. Preferred preservatives are, for example, antioxidants, suchas ascorbic acid, or microbicides, such as sorbic acid or benzoic acid.

EXAMPLES General Methods and Materials

Compounds and chemicals were of purest possible grade. Anandamide (AEA),(R)—N-(1-(4-hydroxyphenyl)-2-hydroxyethyl)oleamide (OMDM-2),N-(3-furanylmethyl)-(5Z,8Z,11Z,14Z)-eicosatetraenamide (UCM707),[ethanolamine-1-3H]-AEA (60 Ci/mmol) was purchased from AmericanRadiolabeled Chemicals. Albumin from bovine serum essentially fatty acidfree (BSA) (A7030), fetal bovine serum (F7524), RPMI-1640 were purchasedfrom Sigma-Aldrich, Germany. AquaSil™ siliconizing fluid was purchasedfrom Thermo Scientific.

[³H]-AEA Cellular Uptake

Screening for AEA cellular uptake inhibition was performed in asemi-automated procedure: Pipetting and washing steps were performed bya Biomek3000 laboratory workstation. First, required amounts of U937cells were centrifuged at 100×g for 5 min and resuspended in RPMI (37°C.) to a final concentration of 2×10⁶ cells/mL. Then, 250 μL of cellsuspension (0.5×10⁶ cells per sample) were transferred into AquaSil™silanized glass vials (Chromacol 1.1-MTV) in 96-well format. Afteraddition of 5 μL vehicle (DMSO) or compounds the cells were incubated at37° C. for 15 min. As positive controls OMDM-2 and UCM707 were used at10 μM in each run. The ETI-T compounds were measured at up to 7concentrations in triplicates from 100 pM-100 μM. After pre-incubation,a mixture of 0.5 nM[ethanolamine-1-³H]-AEA, (60 Ci/mmol) and 99.5 nM ofcold AEA (final 100 nM) was added and samples were incubated at 37° C.for another 15 min. The reaction was stopped by rapid filtration overUniFilter-96 GF/C filters (PerkinElmer) pre-soaked with PBS 0.25% BSA.Cells were washed three times with 100 μL ice-cold PBS buffer containing1% fatty acid free BSA. After drying, 45 μL MicroScint 20 scintillationcocktail (PerkinElmer, Waltham, Mass., US) was added to the wells andthe plate was sealed. Radioactivity was measured by liquid scintillationcounting on a PerkinElmer Wallac Trilux MicroBeta 1450 during 2 min.Non-specific binding of [³H]AEA (100 nM) to the glass vials was neverhigher than 10%. IC₅₀ values were calculated by GraphPad® by non-linearregression using the built-in log(inhibitor) vs. response-variable slope(four parameters) function.

FAAH Activity

Hydrolysis of [³H]-AEA by FAAH was determined as previously described incell homogenates of U937 cells (0.18 mg protein) (Omeir et al., 1999,Biochem Biophys Res Commun, 264, 316-20; Mor et al., 2004, J Med Chem,47, 4998-5008). Protein amounts of cell homogenates corresponded to0.5×10⁶ cells (U937), to assure best possible comparability of IC₅₀values as used for the AEA cellular uptake assays. URB597 was used aspositive control. Protein quantification was performed using a BCA assay(Thermo Scientific). Enzyme activity was assessed by addition of vehicleor compounds in 10 μL DMSO to 490 μL homogenate in 10 mM Tris HCl, 1 mMEDTA, 0.1% (w/v) BSA fatty acid free, pH=8 and incubation for 15 min at37° C. After, a mixture of AEA plus [ethanolamine-1-³H]-AEA (0.5 nM) atfinal 100 nM was added to the homogenates and incubated for 15 min at37° C. The reaction was stopped by addition of 1 mL ice-cold CHCl₃:MeOH(1:1) followed by vigorous vortexing. Phase separation was achieved bycentrifugation at 10'000×g at 4° C. for 10 min. Radioactivity of theseparated aqueous phase (upper phase) containing [³H-ethanolamine] or[³H-glycerol] was measured by liquid scintillation counting on aTri-Carb 2100 TR liquid scintillation analyzer after addition of 3.5 mLUltima Gold scintillation cocktail (PerkinElmer Life Sciences). Resultsare expressed as hydrolysis of tritium substrate in percent of vehicletreated control. IC₅₀ values were calculated by GraphPad®. Data arereported as means of n=3 independent experiments performed intriplicates.

Radioligand CB Receptor Binding

Binding properties of ETI-T compounds to hCB1 or hCB2 receptors wereperformed as previously reported in a [³H]-CP55,940 displacement assay(Gertsch et al., 2008, Proc Natl Acad Sci 105, 9099-104). WIN 55,212-2was used as positive control. In brief, 20 μg protein of CHO-K1 hCB₁ orhCB₂ membrane preparations were thawed on ice and resuspended in a finalvolume of 500 μL binding buffer (50 mM Tris-HCl, 2.5 mM EDTA, 5 mMMgCl2, 0.5% fatty acid free BSA, pH 7.4) in silanized glass vials.[³H]-CP55,940 (168 Ci/mmol) (PerkinElmer, Waltham, Mass., US) was addedto a final concentration of 0.5 nM followed by the addition ofcompetitors or vehicle in 5 μL DMSO. Membrane binding was equilibratedfor 2 h at room temperature (25° C.). Samples were filter through a 0.1%polyethylenimine pre-soaked UniFilter®-96 GF/B plate (PerkinElmer) andwashed twelve times with 167 μL ice-cold assay-buffer. The plate wasdried, bottom sealed and 45 μL MicroScint 20 scintillation cocktail(PerkinElmer) were added before measured on a PerkinElmer 1450 MicrobetaTRILUX liquid scintillation counter. Unspecific binding was determinedby WIN 55,212-2, 10 μM and subtracted from all values. IC₅₀ values.

General Synthesis

The compounds of the invention may be produced according to one of thepathways depicted in scheme 1 or scheme 2. The starting materials may bepurchased or produced according to literature procedures.

Evaluation:

TABLE 1 AEA uptake inhibition AEA uptake inhibition IC50 Compound (μM)

0.731

0.194

2.3

7.1

15.6

6.7

6.6

1.6

5.5

1.0

2.78

0.817

3.36

0.729

2.12

5.56

3.26

9.94

0.515

4.63

11.77

0.291

0.180

3.24

2.34

0.170

5.10

0.440

2.80

6.92

1.74

1.69

0.135

0.111

0.257

1.45

0.107

2.14

1.59

0.164

2.73

16.6

1.07

0.610

0.677

0.879

0.557

1.84

0.657

1.31

1.09

5.42

4.15

1.81

2.29

7.18

2.27

3.18

TABLE 2 AEA uptake inhibition of further compounds ETI-T- AEA uptakeETI-T- AEA uptake compound IC50 (μM) compound IC50 (μM) 24_Q_B 0.03324_N_A 0.334 24_Q_I 0.035 24_Q_N 0.373 24_P_L 0.051 24_B_N 0.419 24_Q_L0.085 24_N_I 0.462 24_P_I 0.087 24_P_X 0.509 24_Q_X 0.137 24_P_N 0.5324_A_B 0.138 24_A_L 0.616 24_B_I 0.141 24_B_L 0.663 24_B_X 0.162 24_N_B0.667 24_Q_A 0.164 24_A_X 0.721 24_B_B 0.170 24 0.817 24_C_N 0.17024_F_N 0.939 24_N_X 0.172 24_P_B 1.043 24_B_A 0.176 24_S_N 1.43 24_P_A0.176 24_A_N 1.510 24_A_A 0.286 24_K_N 1.620 24_A_I 0.301

TABLE 3 FAAH inhibition of further compounds FAAH FAAH ETI-T- inhibitionETI-T- inhibition compound IC50 (μM) compound IC50 (μM) 24_Q_B 1.28824_N_A >100 24_Q_I 0.037 24_Q_N 0.437 24_P_L 0.617 24_N_I >100 24_Q_L0.813 24_P_X 2.63 24_P_I 0.170 24_P_N 0.912 24_Q_X 0.427 24_N_B >10024_B_I >100 24 >100 24_B_X >100 24_F_N >100 24_Q_A >100 24_P_B 11.2224_B_B >100 24_C_B >100 24_C_N 1.585 24_C_C >100 24_N_X >100 24_C_F >10024_P_A 1.514 22_B_I >100 24_A_A >100 24_A_I >100

TABLE 4 CB1 receptor binding of further compounds CB1 receptor CB1receptor ETI-T- binding % ETI-T- binding % compound at 10 μM compound at10 μM 24_Q_B 45 24_A_I 58 24_Q_I 47 24_N_A 80 24_P_L 41 24_Q_N 26 24_Q_L44 24_B_N 53 24_P_I 61 24_N_I 82 24_A_B 29 24_P_X 78 24_B_I 42 24_P_N 5224_B_X 78 24_A_L 67 24_Q_A 74 24_B_L 63 24_B_B 3 24_N_B 86 24_C_N 6824_A_X 54 24_N_X 43 24 1 24_B_A 32 24_P_B 50 24_P_A 83 24_S_N 56 24_A_A30 24_K_N 78 22B_I 42

TABLE 5 AEA uptake inhibition of further compounds ETI-T- AEA uptakeETI-T- AEA uptake compound IC50 (μM) compound IC50 (μM) 04_A_N 0.10703_C_K 0.564 04_B_I 0.132 03_N_K 0.564 04_K_N 0.142 04_B_X 0.578 04_A_X0.155 03_N_C 0.610 04_F_N 0.164 32_B_A 0.632 04 0.194 03_N_G 0.67703_T_N 0.262 03_C_O 0.727 32 0.291 04_N_K 0.727 03_A_A 0.315 03 0.73132_A_X 0.327 03_B_A 0.760 32_A_I 0.341 04_C_B 0.861 28_A_X 0.351 04_S_N0.878 28_A_I 0.389 03_N_M 0.879 04_A_A 0.390 32_B_X 0.993 03_P_N 0.40304_P_N 1.020 03_B_X 0.479 04_C_G 1.060 04_C_F 0.484 03_F_N 1.070 03_U_N0.509 04_C_O 1.120 28 0.515 04_C_K 1.140 04_B_A 0.527 04_U_N 1.4 04_N_G0.557 04_D_N 1.590

TABLE 6 FAAH inhibition of further compounds FAAH FAAH FAAH ETI-T-inhibition ETI-T- inhibition ETI-T- inhibition compound IC50 (μM)compound IC50 (μM) compound IC50 (μM) 04_A_N >100 03_T_N >10028_A_I >100 04_B_I 22.909 32 >100 04_A_A >100 04_K_N >100 03_A_A >10003_P_N <10 04_A_X 14.454 32_A_X >100 03_B_X >100 04_F_N >100 32_A_I >10004_C_F >10 04 >100 28_A_X >100

TABLE 7 CB1 receptor binding of further compounds CB1 CB1 CB1 receptorreceptor receptor ETI-T- binding % ETI-T- binding % ETI-T- binding %compound at 10 μM compound at 10 μM compound at 10 μM 04_A_N 71 03_T_N36 28_A_I 31 04_B_I 43 32 37 04_A_A 49 04_K_N 80 03_A_A 57 03_P_N 7104_A_X 27 32_A_X 55 03_B_X 46 04_F_N 55 32_A_I 43 04_C_F 27 04 43 28_A_X51

TABLE 8 AEA uptake inhibition of further compounds AEA AEA AEA ETI-T-uptake ETI-T- uptake ETI-T- uptake compound IC50 (μM) compound IC50 (μM)compound IC50 (μM) 22_K_N 0.097 22_U_N 0.812 22_R_N 5.180 22_A_N 0.11122_N_K 0.861 22_C_C 10.420 22_B_X 0.127 15 1.030 23_A_V 10.500 22_F_N0.135 22_N_G 1.090 22_B_V 12.540 22_A_X 0.150 22_C_O 1.200 15_U_N 15.55022_A_A 0.341 22_C_G 1.280 34 >10 15_Q_N 0.368 22_N_M 1.310 04_A_V >1022_B_A 0.386 22_C_K 1.430 15_R_N >10 22_P_N 0.500 22_D_N 1.45022_A_V >10 22_C_F 0.592 15_C_O 1.560 22_E_N >10 22_N_C 0.657 22_C_N1.660 22_N_F >10 15_C_K 0.692 15_C_N 1.690 22_T_N >10 22_Q_N 0.71322_C_B 2.170 22 0.729 15_T_N 2.640

Table 9 and 10—FAAH Inhibition and CB1 Receptor Binding of FurtherCompounds

FAAH ETI-T- inhibition compound IC50 (μM) 22_K_N 6.607 22_A_N 19.49822_B_X 19.055 22_F_N >100 22_A_X >100 22_A_A >100 15_Q_N <10 22_B_A >100

CB1 receptor ETI-T- binding % compound at 10 μM 22_K_N 63 22_A_N 7122_B_X 70 22_F_N 33 22_A_X 41 22_A_A 50 15_Q_N 27 22_B_A 24

TABLE 11 AEA uptake inhibition, FAAH inhibition andCB1 receptor bindingof further compounds CB1 AEA FAAH receptor ETI-T- uptake ETI-T-inhibition ETI-T- binding % compound IC50 (μM) compound IC50 (μM)compound at 10 μM 23_C_N 0.180 23_C_N >10 23_C_N 75 23_T_N 0.556 23_Q_N0.598 23_C_G 0.753 23_N_K 1.120 23_B_X 1.132 23_C_O 1.190

We claim:
 1. A compound comprising formula (1)

wherein R1 is selected from formula 2b′, 2c′, 2g′ or 2h′,

with D being a C1 to C4 alkyl, or R1 is selected from 2b, 2c 2g or 2h

with T′ being selected from —CH2, —NH, —S, —O, —CHCH3, —C(CH3)2 or —NRc,and with each T″ being selected independently from each other from beingselected from —CH or ═N, with R6 being selected from —OH, —OCH3,—OCH2CH3, —CH3 or H, with n of Z1n being 0, 1, 2 or 3, and with each Z1independently from any other Z1 being selected from —F, —Cl, —Br, —I,CN, —Ra, —ORa, —(CH2)rORa, —SRa, —(CH2)rSRa or —NRa2, with each Ra beingselected independently from each other from H, a substituted orunsubstituted C1-C8 alkyl, a substituted or unsubstituted C2-C8 alkenyl,or a substituted or unsubstituted C2-C8 alkynyl, with r being 1, 2, 3 or4, with Rc being —CH2OH, —CH3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2, —CH2CF3,—CHFCF3, —CF2CF3, —CHF2, —CH2F, —CF3, and each of R2 and R3 are selectedindependently from each other from a substituted or unsubstituted alkyl,a substituted or unsubstituted alkoxy, a substituted or unsubstitutedalkenyl, a substituted or unsubstituted alkynyl, a substituted orunsubstituted cycloalkyl, a substituted or unsubstituted aryl, asubstituted or unsubstituted saturated heterocycle, or a substituted orunsubstituted heteroaryl,
 2. The compound according to claim 1, whereinR2 selected from a substituted or unsubstituted alkyl, a substituted orunsubstituted alkenyl, a substituted or unsubstituted alkynyl, asubstituted or unsubstituted cycloalkyl, a substituted or unsubstitutedaryl, or a substituted or unsubstituted heteroaryl.
 3. The compoundaccording to claim 1, wherein R2 is selected from a substituted alkyl,alkenyl or alkynyl, wherein the substituted alkyl, alkenyl or alkynylcomprises the formula -L-Ar, with L being an alkyl, an alkenyl, analkynyl, and Ar being a substituted or unsubstituted C5-C6— aryl or asubstituted or unsubstituted C5-C6— heteroaryl, or a substituted orunsubstituted C6— aryl or a substituted or unsubstituted C5-C6—heteroaryl.
 4. The compound according to claim 1, wherein R2 is selectedfrom a substituted alkyl, alkenyl or alkynyl, wherein the substitutedalkyl, alkenyl or alkynyl comprises the formula 4a

or a substituted or unsubstituted C6— aryl, wherein the substituted C6aryl comprises the formula 4b

with L being an alkyl, an alkenyl, an alkynyl, and o of Z²o is 0, 1, 2,3, 4 or 5, and each Z² independently from any other Z² is selected from—F, —Cl, —Br, —I, CN, —Rb, —ORb, —(CH2)rORb, —SRb, —(CH2)rSRb or —NRb2,with each Rb being selected independently from each other from H, asubstituted or unsubstituted C1-C12 alkyl, a substituted orunsubstituted C2-C12 alkenyl, or a substituted or unsubstituted C2-C12alkynyl, with r being 1, 2, 3 or
 4. 5. The compound according to claim4, wherein o of Z²o is 0, 1, 2, 3, 4 or 5, and each Z² is selectedindependently from any other Z² from —F, —Cl, —Br, —I, CN, —Rb, —ORb,CH2ORb or —NRb2, with each Rb being selected independently from eachother from H, a substituted or unsubstituted C1-C12 alkyl, a substitutedor unsubstituted C2-C12 alkenyl or a substituted or unsubstituted C2-C12alkynyl.
 6. The compound according to claim 5, wherein o of Z²o is 0, 1,2, 3, 4 or 5, and each Z² is selected independently from any other Z²from —F, —Cl, —Br, —I, CN, —Rb, —ORb, CH2ORb or —NRb2, with each Rbbeing selected independently from each other from H, a substituted orunsubstituted C1-C12 alkyl, a substituted or unsubstituted C2-C12alkenyl or a substituted or unsubstituted C2-C12 alkynyl.
 7. A methodfor administering to a subject in need thereof the compound of claim 1,inhibiting N-arachidonoylethanolamine uptake in a subject, comprisingadministering to a subject in need thereof a therapeutically effectiveamount of a compound of claim 1, thereby treating the disorder.
 8. Themethod according to claim 7, wherein the subject has a disorder selectedfrom the group consisting of a psychiatric disorder, a neurologicaldisorder and neuroinflammation comprising: administering to a subject inneed thereof a therapeutically effective amount of the compoundaccording to claim 1, thereby treating the psychiatric, neurologicaldisorders or neuroinflammation.
 9. A method for inhibitingN-arachidonoylethanolamine uptake in a subject, comprising administeringto a subject in need there of a therapeutically effective amount of acompound of claim 1, thereby inhibiting N-arachidonoylethanolamineuptake in the subject.